Radiographs presented as part of the 1997 ACVR Oral Certification Examination Musculoskeletal Section.
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Biomedical subjects
Publications and source records attributed to G B Daniel.
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The extraction of the hepatobiliary radiopharmaceutical 99mTc-mebrofenin (Choletec) by the liver can be used to evaluate the severity of hepatocellular disease. The hepatic parenchymal cells extract mebrofenin from the blood by the same active transport mechanism as bilirubin. The ability of the liver to extract 99mTc-mebrofenin is a measure of hepatic parenchymal cell function. In this study, we induced hepatocellular disease by administration of a hepatotoxic drug and compared a direct method of determining the hepatic extraction of 99mTc-mebrofenin to hepatic extraction fraction derived from deconvolutional analysis. We also compared both methods of calculating the hepatic extraction of 99mTc-mebrofenin to liver histopathology. Hepatic extraction fraction derived from deconvolutional analysis correlated very well to the direct measurement technique (R=0.922, p < 0.001). Both methods of determining hepatic extraction correlated well to quantitative histopathology, having the same correlation coefficient and p values. (R=-0.833, p=0.003). As the hepatic extraction 99mTc-mebrofenin decreased, the severity of the histopathologic lesions of the liver increased in a linear fashion. There was a significant correlation of the hepatic excretion T1/2 to quantitative histopathology (R=0.949, p < 0.001). The hepatic excretion T1/2 increased as the severity of the histopathologic lesions of the liver increased. Hepatic extraction (HEF) and excretion of 99mTc-mebrofenin are good predictors of the severity of hepatocellular damage in toxic induced liver disease. This study helps validate the premise that HEF derived from deconvolutional analysis is a good predictor of the actual first pass hepatic extraction of 99mTc-mebrofenin.
The feasibility and reproducibility of obtaining the pulsed-wave Doppler measurements of resistive index (RI) and pulsatility index (PI) were investigated in intrarenal arteries of normal, nonsedated cats, and cats anesthetized with isoflurane. In addition, relative renal function and relative renal blood flow were evaluated using quantitative renal scintigraphy. The percentage of injected dose uptake, time to peak activity, and two indices of renal blood flow (K/A ratio and flow index) obtained during the first pass of 99mTc-MAG3, were determined for both awake and anesthetized cats. Results indicate that measuring RI and PI in nonsedated cats is readily accomplished and that the results are reproducible within an animal. Mean RI and PI values in the awake cats were 0.55 and 0.8, respectively. Significant differences between the awake and anesthetized cats were found for all pulsed-wave Doppler and quantitative renal scintigraphic measurements evaluated.
Radionuclide ventriculography has been used in humans to evaluate valvular incompetency. The stroke volume ratio, derived from the radionuclide ventriculogram, is used to quantify the severity of mitral regurgitation (MR). Previous studies conducted in humans have shown that left to right stroke volume ratio increases as the severity of MR increases. In this study, we evaluated radionuclide ventriculography as a noninvasive method to detect MR in dogs with surgically created mitral insufficiency. Six male and three female adult, conditioned mongrel dogs were used. Scintigraphic studies were performed prior to and 4 weeks after surgically created MR. Because of the overlap of the left and right ventricles when viewed from a left lateral position, we combined data from a first-pass radionuclide angiocardiogram with the radionuclide ventriculogram to obtain a corrected stroke volume ratio. Blood flow transit parameters were also derived from the first-pass radionuclide angiocardiogram. Standard left ventricular functional indices were also measured from the radionuclide ventriculogram. On the left lateral view of the heart, 25 to 30% of the right ventricular volume overlaps the left ventricle. After correcting for the overlap, the stroke volume ratio of normal dogs was 1.17+/-0.178 (mean+/-SD), which increased to 2.06+/-0.41 (mean+/-SD) (p < .001) 4 weeks after creation of MR. The was no significant change in left ventricular ejection fraction or peak rate of ejection following MR. The transit times of blood through the left ventricle were measured from the first-pass radionuclide angiocardiogram and were expressed as half-time clearance, peak clearance rate, and time to peak clearance rate. The baseline half-time clearance was 2.07+/-0.71 s (mean+/-SD), which increased to 6.70+/-4.89 s (mean+/-SD) (p = .02) after creation of MR. The baseline peak clearance rate was 49.75+/-8.96 cts/s (mean+/-SD), which decreased to 23.12+/-6.84 cts/s (mean+/-SD) (p < .001) after creation of MR. Stroke volume ratios significantly increased following creation of MR. Blood flow transit through the left ventricle slowed following creation of MR. The variability of these parameters were small in the baseline studies, suggesting these techniques may be clinically useful to gauge the severity of MR in dogs.
Renal nuclear medicine is used to evaluate renal function and morphology. Renal scintigraphy is the best imaging modality for evaluation of functional parameters such as glomerular filtration rate and effective renal plasma flow. The commonly used renal radiopharmaceuticals are reviewed. Both imaging and non-imaging techniques are presented. Specific applications of renal nuclear medicine are discussed.
In this study, plasma time-activity curves of 99mTc-mebrofenin were used to quantify hepatic function in dogs before and after induction of hepatic damage using a hepatotoxic agent. Nine dogs were determined to be healthy on the basis of physical examination, laboratory data and hepatic imaging. Plasma samples were collected 1, 3, 5, 7, 9, 15, 20, 30, 40, 50, and 60 minutes following a peripheral venous injection of 111-222 MBq (3-6 mCi) of 99mTc-mebrofenin. The area under the plasma time-activity curve (AUC) was calculated using two different methods and compared to direct measurement of the hepatic extraction efficiency. First pass hepatic extraction efficiency of 99mTc-mebrofenin was calculated from differential equation analysis of a two-compartment model following mesenteric venous injection of the radiopharmaceutical. In 7 of the original 9 dogs and 2 additional healthy dogs, plasma clearance and hepatic extraction efficiency determination were repeated following induction of hepatic injury by thiacetarsamide (3 mg/kg IV twice daily for 1 day). In one additional dog, hepatic injury was induced using carbon tetrachloride (0.3 ml/kg IP). Plasma time-activity curves of 99mTc-mebrofenin had kinetics of a two compartment model. Area under the curve was highly correlated with hepatic extraction efficiency. The AUC integrated from 1-60 minutes (AUC60) had the best correlation with hepatic extraction efficiency (r2 = 0.978, p < 0.001). A formula for calculation of hepatic extraction efficiency was derived using linear regression analysis: hepatic extraction efficiency = 105.583 - 3.099 x 10(5) x AUC60. Plasma clearance of a peripheral venous injection of 99mTc-mebrofenin is a simple, non-invasive, convenient method to quantify hepatic function which can be performed without a gamma camera.
The purpose of this study was to evaluate the utility of double-phase parathyroid scintigraphy using 99mTc-sestamibi for detecting and localizing hyperfunctioning parathyroid glands in hypercalcemic dogs. Fifteen hypercalcemic dogs that underwent parathyroid scintigraphy were included in this study: 3 dogs with hypercalcemia of malignancy, and 12 dogs with hyperfunctioning parathyroid tissue (parathyroid adenoma or parathyroid hyperplasia). The presence of parathyroid adenoma or parathyroid hyperplasia was documented by histopathologic examination. In 3 dogs with hypercalcemia of malignancy, parathyroid scintigraphy was negative for hyperfunctioning parathyroid tissue and the scans were classified as true negative. Parathyroid scintigraphy correctly identified the presence and location of hyperfunctioning parathyroid tissue in only 1 of 6 dogs with a parathyroid adenoma. False positive and false negative results occurred in dogs with parathyroid adenomas. Parathyroid scintigraphy failed to detect hyperfunctioning parathyroid tissue in 5 of 6 dogs with parathyroid hyperplasia and were classified as false negative. False positive results were obtained in the remaining dog with parathyroid hyperplasia. Sensitivity of parathyroid scintigraphy for detecting and localizing hyperfunctioning parathyroid tissue was 11%, specificity was 50%, and overall accuracy was 27%. Positive and negative predictive value were 25% and 27%, respectively. Sensitivity for detection of parathyroid adenomas was 25%, and sensitivity for detection of hyperplastic glands was 0 %. Results of this study indicate that double-phase parathyroid scintigraphy does not appear to have acceptable accuracy in detecting hyperfunctioning parathyroid glands in dogs. Due to the poor sensitivity and specificity of the technique in dogs, parathyroid scintigraphy is not recommended for definitive identification of abnormal parathyroid glands as the cause of hypercalcemia in dogs.
Gated radionuclide ventriculography was evaluated as a noninvasive method of quantifying right ventricular function in dogs with experimentally induced congestive heart failure. Gated radionuclide ventriculography measurements of right ventricular function (right ventricular ejection fraction, right ventricular average emptying rate, and right ventricular average filling rate) were related to standard hemodynamic and echocardiographic measurements. Congestive heart failure was induced by rapid ventricular pacing in eight normal dogs. Hemodynamic, echocardiographic, and gated radionuclide ventriculography measurements were obtained before and after development of biventricular failure. Congestive heart failure resulted in significant changes in all hemodynamic, echocardiographic, and gated radionuclide ventriculography measurements with the exception of systemic arterial pressure. Right ventricular ejection fraction was inversely related to pulmonary artery systolic, diastolic, and mean pressure, and right ventricular average emptying rate was inversely related to the pulmonary artery systolic, diastolic, and mean pressure. Right ventricular ejection fraction was inversely related to left ventricular filling pressure, (pulmonary capillary wedge pressure). Neither the echocardiographic measurements of right ventricular size (right ventricular internal diastolic dimension) nor the right ventricular end-diastolic pressure were related to right ventricular ejection fraction and right ventricular average emptying rate. However, echocardiographic measurements of right ventricular dimension were related to right ventricular filling pressure. The gated radionuclide ventriculography indexes of right ventricular function, right ventricular ejection fraction and right ventricular average emptying rate, are affected by afterload but unaffected by preload, whereas the echocardiographic measurement of right ventricular dimension is related to preload. Gated radionuclide ventriculography provides right ventricular data which is unique from that obtained by standard echocardiographic imaging. Also, gated radionuclide ventriculography has potential value as a noninvasive means of estimating a change in pulmonary artery pressure.
In this study, heart time-activity curve, created following intravenous injection of 99mTc-mebrofenin were used to quantify hepatic function in normal dogs and dogs with induced hepatic parenchymal cell damage. The results were compared to a direct measurement of hepatic extraction following mesenteric venous injection of 99mTc-mebrofenin. The heart time-activity curves were normalized and the area under the curve from 0-30 minutes and 0-60 minutes were determined. In addition, the half-time clearance rate of the heart time-activity curve was analyzed using a two-compartment model. Linear regression analysis was used to describe the relationship between the area under the normalized heart time-activity curve and hepatic extraction. There was good correlation between the area under the normalized heart time-activity curve and hepatic extraction. The best correlation was obtained from the 0-30 minute data (r2 = 0.92). A formula for calculating hepatic extraction was derived using linear regression analysis: Hepatic extraction = 1.092 - (0.0000308 x AUC0-30 minutes). There was good correlation between the half-time clearance rates from the heart time-activity curve and hepatic extraction. The best correlation was between the fast phase half-time clearance and hepatic extraction (r2 = 0.88). The area under a normalized heart time-activity curve can be used as a simple alternative to deconvolutional analysis for the determination of hepatic extraction as a measure of hepatic parenchymal cell function in the dog.
Many hyperthyroid cats referred for thyroid imaging and 131I therapy are concurrently or recently receiving antithyroid medications. The effect of the antithyroid drug, methimazole, on thyroid uptake of 99mTcO4 and 123I was evaluated in 8 normal cats. Quantitative analysis was used to determine the normal percent dose uptake of 99mTcO4 and 123I, the change in thyroid:salivary ratios (T:S) of 99-TcO4 over time, and the duration of the methimazole effect on thyroid uptake of 123I. Methimazole was administered to 5 cats for 3 weeks in which a hypothyroid state was obtained; 3 cats served as non-treatment controls. 99mTcO4 and 8 and 24 hour 123I imaging was repeated after 3 weeks of methimazole therapy (time of maximum T4 suppression). Methimazole was then discontinued and 123I images and serum T4 concentrations were repeated at 1, 4, 9, 15, and 24 days post withdrawal. The percent dose uptake of 99mTcO4 increased throughout the acquisition period with maximum uptake occurring 4 hour post injection. The baseline 20 min. T:S ratio for controls and treatment cats were 0.79 +/- 0.08 and 0.81 +/- 0.05 respectively; with a peak value of 1.29 +/- 0.23 and 1.31 +/- 0.18 at 4 hours. The baseline T:S ratios were not significantly different from 20 minutes to 2 hours, however they were significantly elevated at 4 hours post injection. Baseline, 8 and 24 hour percent dose uptake of 123I were 2.1 +/- 0.42% and 7.04 +/- 1.24%, respectively. There was a significant increase in the T:S ratio in the treatment group at all time points. The 8 hour percent dose uptake of 123I at 1, 4, and 9 days post methimazole withdrawal were significantly increased and peaked at 4 days. The 24 hour uptake was significantly increased at 4 and 9 days, with peak uptake at 9 days post-methimazole withdrawal. The 123I percent dose uptake decreased to baseline values by day 15 post withdrawal. Radioiodine uptake is not inhibited by methimazole treatment in normal cats, and is significantly enhanced after recent withdrawal. This finding is supportive of a "short term rebund effect" with maximal enhanced uptake between 4 and 9 days after discontinuing antithyroid drugs. The increased uptake of 99mTcO4 may also affect the interpretation of 99mTcO4 thyroid scintigraphy for 2-3 weeks.
Per rectal portal scintigraphy using 99mTechnetium pertechnetate (99mTcO4-) was used to diagnose portosystemic shunts (PSS) before surgical confirmation in seven dogs and two cats. Shunt fractions, representing the percent of portal blood that bypasses the liver, were determined by computer analysis of the scintigraphic images. Animals with portosystemic shunts had a mean preoperative shunt fraction of 84.02% (n = 9). The mean postoperative shunt fraction in four animals was 58.22%. The mean shunt fraction in ten control dogs was 5.00%. Per rectal portal scintigraphy is an innovative, easily performed, inexpensive method to diagnose congenital portosystemic shunts in dogs and cats.
Three cats were diagnosed as hyperthyroid based on clinical signs, historical findings, laboratory abnormalities, and basal serum thyroxine (T4) concentrations, and/or nuclear thyroid scans. Additionally, a presumptive diagnosis of thyroid carcinoma with pulmonary metastasis was made in each cat based on radiographic or scintigraphic evaluation. All three cats had solitary pulmonary nodules 1.5 to 2 cm in diameter on survey thoracic radiographs; one cat also had chylous pleural effusion and pulmonary lobar consolidation. Focal pulmonary accumulation of sodium pertechnetate (99mTcO4-) and/or radioiodine (131I) corresponding to radiographic lesions were seen in all cats. Two cats were treated with single ablative doses (1111 to 1480 MBq) of 131I; the remaining cat was euthanatized. One of the treated cats died 8 days later; the other cat was euthanatized 22 weeks following treatment. Histopathologic examination of tissue obtained at necropsy confirmed metastatic thyroid carcinoma in one cat and bronchogenic adenocarcinoma in two cats. Our findings indicate that increased radionuclide uptake in focal pulmonary lesions and cytologic evaluation of tissue obtained by fine-needle aspiration are not specific for thyroid tissue.