Limitations of ultrasound for measuring gallbladder bile emptying and refilling.
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Cholecystokinin↗
Biomedical subjects
G T Krishnamurthy
Publications and source records attributed to G T Krishnamurthy.
Importance of precise determination of technetium-labeled DISIDA concentrations for in vitro hepatocellular transport studies.
Technetium 99m-labeled diisopropyliminodiacetic (acid [99mTc]DISIDA) has been used extensively in the evaluation of hepatobiliary diseases. As a result of investigation into transport mechanisms of [99mTc]DISIDA, we undertook to determine precise concentrations of this compound in the standard clinical formulation. Calculations based on published formulas were used. These take into account column efficiency, the time since the previous elution of 99mTc from the 99Mo column, and the total quantity of 99mTc eluted. Primary cultures of rat hepatocytes were used to evaluate the transport of Na99mTcO4 and the 99mTc-labeled DISIDA monomer. Pertechnetate was not taken up by the hepatocytes, the amount of [99mTc]DISIDa taken up was not dependent on the concentration of DISIDA but rather on the concentration of technetium, when the DISIDA/99mTc ratio was varied in the culture medium. We conclude that calculation of the total technetium concentration is necessary to determine the amount of compound taken up by the liver, and to interpret kinetic studies of hepatocellular transport mechanisms.
Animals↗
Gallbladder ejection fraction: a decade of progress and future promise.
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Gallbladder Diseases↗
Identification and differentiation of congenital gallbladder abnormality by quantitative technetium-99m IDA cholescintigraphy.
Failure to visualize the gallbladder in its usual location along the right inferior hepatic border suggests many possibilities including acute cholecystitis. The case described here reveals the importance of proper protocol for hepatobiliary imaging with 99mTC-IDA agents, the necessity of quantification of function as an integral part of imaging to enable proper differential diagnosis. A case of bilobed gallbladder presenting as a Valentine heart in an unusual location in the liver is described. The measurement of the CCK-8 induced gallbladder ejection fraction for each lobe facilitated proper diagnosis.
Adult↗
Technetium-99m monoclonal antibody fragment (Fab) scintigraphy in the evaluation of small cell lung cancer: a preliminary report.
Small cell lung cancer (SCC) has the most rapid growth rate of the four cell types and metastasizes early. Present imaging modalities for staging include chest x-ray, CT, MRI and bone scans. In this preliminary study, we assessed the clinical role of 99mTc-monoclonal antibody (MOAB) scintigraphy in five patients with histologically proven SCC. Each patient was infused with 20-30 mCi of 99mTc labeled Fab fragment of MOAB (NR-LU-10, NeoRx, Seattle, Wash.). Total body simultaneous anterior and posterior images were obtained 14-16 h post injection. SPECT images of the chest were obtained through a 360 degrees rotation of the gamma camera and recorded on a 62 x 64 x 16 matrix. Images (1.2 cm thick) were generated in transaxial, sagittal and coronal views. Fourteen of fifteen chest lesions detected by CT were confirmed by 99mTc MOAB scintigraphy. Scintigraphy detected one additional chest lesion not seen by CT. Scintigraphy failed to detect a brain lesion (2 cm), a chest lesion, and two adrenal lesions, all of which were seen by CT. In one patient with multiple (more than 10) lesions in the liver, both scintigraphy and CT detected all lesions. Three spine lesions seen on 99mTc MDP scan and positive for metastasis on MRI concentrated 99mTc MOAB, but two rib lesions seen on 99mTc MDP bone scan did not concentrate 99mTc MOAB. It is concluded from these preliminary results that the potential usefulness of 99mTc MOAB scintigraphy as a complementary imaging modality in the staging of small cell lung cancer should be investigated further.
Bone Marrow↗
Quantification of hepatobiliary function as an integral part of imaging with technetium-99m-mebrofenin in health and disease.
A study was undertaken to check the feasibility of measuring the hepatic extraction fraction (HEF) and excretion T-1/2 values as an integral part of hepatobiliary imaging with technetium-99m-mebrofenin in health and disease. In 18 controls subjects, the HEF was 100% and the T-1/2 excretion mean +/- s.e. value was 15.23 +/- 1.4 min. The mean appearance times of the common bile duct (CBD), gallbladder (GB), and small intestine were 15.8 +/- 1.52, 20.2 +/- 2.7, and 23.8 +/- 3.08 min, respectively. Rising serum bilirubin in patients decreased HEF and increased T-1/2 excretion value resulting in delayed appearance of CBD, GB, and small intestine. In control subjects and patients with bilirubin less than 5 mg%, T-1/2 excretion values at 30, 40, and 50 min were similar to those values calculated using the entire 60 min of data, suggesting that the hepatic phase study time could be reduced to 30-40 min and still use the normal reference values established for 60 min. In patients with bilirubin greater than 5 mg%, the data collection duration should be continued for 60 min.
Aniline Compounds↗
Evaluation of primary lung cancer with indium 111 anti-carcinoembryonic antigen (type ZCE-025) monoclonal antibody scintigraphy.
A study was undertaken to test whether indium 111 (111In)-labeled anti-carcinoembryonic antigen (CEA) (type ZCE 025) monoclonal intact antibody (MoAb) would concentrate in primary lung cancer enabling its detection and localization by scintigraphy. The scintigraphic results were correlated with chest radiograph, computed tomograph (CT), bronchoscopy, surgical resection, and tumor CEA analysis. Twenty adult male patients with clinical suspicion of primary lung cancer were studied. Each subject was infused with 4 to 5 mCi of 111In anti-CEA ZCE 025 MoAb, and planar and tomographic scintiphotos were obtained on days 3 and 6 or 7 postinfusion. The scintigraphy was true-positive in 12 of 16 patients with primary lung cancer, eight of nine patients with squamous cell carcinoma, and four of seven with adenocarcinoma; it was true-negative in three of four patients with benign lung disease with an overall accuracy of 75%. In seven patients with confirmed primary lung cancer, but with negative bronchoscopic findings, the scintigraphy was true-positive in four. In 11 patients with definitely positive or suspicious malignancy by bronchoscopy the monoclonal scintigraphy was positive in eight. In true-positive cases, the location and size of the lesion by 111In anti-CEA ZCE 025 MoAb imaging correlated well with CT findings and also tumor mass at surgery. Only one of 12 tumors stained positive for CEA had serum CEA levels greater than 10 ng/ml, indicating nonleakage of the tumor antigen into general circulation in early lung cancer. It is concluded that 111In anti-CEA ZCE 025 MoAb planar and tomographic imaging shows potential to serve as a noninvasive diagnostic test in the evaluation of primary lung cancer. The lung lesion is likely to be malignant if it concentrates 111In anti-CEA ZCE 025 MoAb and benign if it does not. Further studies in large number of patients with suspected primary lung cancer are needed to define the ultimate role for MoAb scintigraphy.
Adenocarcinoma↗
Improved scintigraphic assessment of severe cholestasis with the hepatic extraction fraction.
In previous studies, we found that biliary scintigraphy with technetium-99m-labeled iminodiacetic acid ([99mTc]IDA) provided excellent discrimination between intrahepatic and extrahepatic cholestasis, except in patients with profound cholestasis who had poor visualization of the biliary tree. In this study, we have used deconvolution analysis to determine the hepatic extraction fraction (HEF) of a hypothetical single circulatory pass of [99mTc]IDA. Our hypothesis was that extraction of radionuclide from the blood would be normal in patients with extrahepatic obstruction alone, but would be impaired in patients with intrahepatic disease (IHD). The purpose of this study was to compare the HEF in patients with profound cholestasis (bilirubin greater than or equal to 3.0 mg/dl) due to either IHD or common bile duct obstruction (CBDO). Normal subjects (N = 13) had an HEF of 100%. Patients with CBDO (N = 13) had slightly reduced HEF values (92.8 +/- 3.2%) despite profound hyperbilirubinemia (6.1 +/- 1.0 mg/dl). Patients with IHD (N = 23) had a markedly reduced HEF (43.1 +/- 4.1%) which was significantly lower than patients with CBDO and normal subjects (P less than 0.001). We conclude that the determination of the HEF during biliary scintigraphy is helpful in distinguishing between intrahepatic and extrahepatic disease in patients with hyperbilirubinemia (bilirubin greater than or equal to 3.0 mg/dl).
Bilirubin↗
Design and operation of a nuclear medicine picture archiving and communication system.
Construction of a new Veterans Administration Medical Center provided a unique opportunity to design and implement a state-of-the-art nuclear medicine department in a large teaching and research hospital. The new medical center allowed the acquisition of all new gamma cameras and computer systems without any historical need to patch together a system of old and new equipment. The picture archiving and communication system (PACS) was designed to link five gamma cameras to four image viewing areas, followed by digital archive on an optical disc. The gamma cameras' computers and viewing areas' computers are linked to a central networking computer in a manner that provides nine independent but digitally communicating image computers. Each nuclear medicine computer is capable of acquiring gamma camera data while possibly also performing up to three other simultaneous tasks: analysis of image data, transfer of image data from node to node, and patient database manipulation. The nine image computers each appear to the user as a digital file cabinet, containing various folders, which in turn contain patient studies. To transfer a patient study from one location to another, the user simply queues a transfer request by selecting a file drawer-folder combination for the source and destination locations. It takes only a few seconds to queue a transfer request, and the transfer is complete about a minute later without any further user intervention. A computer genie awakens during the early morning off-hours and performs housekeeping tasks, including movement of patient studies (based on date of acquisition) from active viewing folders to inactive archive folders. All scheduling, workload data, patient image reports, etc, are handled by a patient textual information database system. Patient reports and scheduling information are transmitted to the medical center's central computer where they are made readily available throughout the medical center. The PACS, in clinical use since the spring of 1988, is practical and well-received by technologists, nuclear medicine physicians, and more importantly, our consumer, the referring physicians.
Hospital Information Systems↗
Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents.
Hepatobiliary imaging, introduced first in late 1950s with iodine 131 rose bengal, has undergone major changes since the introduction of technetium 99m-labeled agents in the late 1970s. 99mTc-labeled iminodiacetic acid (IDA) agents, with their high hepatic uptake and fast biliary excretion, provide superior image resolution in addition to supplying simultaneous physiologic parameters quantitatively. The measurement of hepatic extraction fraction by deconvolutional analysis aids in separating hepatocyte from biliary disease. Excretion half-time calculation by nonlinear least square fit provides a quantitative method of analyzing hepatobiliary function and correlates directly with the severity of disease. The measurement of gallbladder ejection fraction, ejection rate, and common bile duct bile reflux index following cholecystokinin, enables quantification of the degree of obstruction to bile flow through the common bile duct. The combined application of morphologic and physiologic parameters enables diagnosis of various hepatobiliary disease, especially in early stages. Quantitative functional parameters not only provide criteria for diagnosis, but also assist in monitoring the therapeutic benefit from drugs and interventional techniques such as endoscopic sphincterotomy or balloon dilation of the obstruction. Biliary dynamic studies with cholecystokinin assist in distinguishing common bile duct dilation without obstruction from dilation with obstruction. Methods of application of 99mTc-IDA agents in quantitative physiologic studies are reviewed and future direction of their use is proposed.
Biliary Tract↗
Diagnosing gallbladder disease.
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Gallbladder↗
Technetium-99m-iminodiacetic acid organic anions: review of biokinetics and clinical application in hepatology.
Technetium-99m-labeled iminodiacetic acid analogs are a new class of organic anions, taken up and secreted by hepatocyte into hepatic bile by a carrier-mediated organic anion pathway. They provide a new dimension in the assessment of pathophysiology and morphology of the hepatobiliary system. The amount of uptake and the rapidity of its elimination from the liver is dependent upon the structural configuration of the agent as well as the functional integrity of the hepatocyte and the patency of the biliary system. The clinical areas for application are wide and include most of the hepatobiliary diseases. Technetium-99m-iminodiacetic acid, an agent well suited for both planar and single photon tomographic scintigraphy, is ideal for early diagnosis prior to anatomical changes in the hepatobiliary system. The data collection directly from the liver provides quantitation of both regional and global liver diseases. The count-based method for measuring gallbladder emptying overcomes the theoretical disadvantages of geometric tests. Biokinetics and current clinical application of six of the 99mTc-iminodiacetic acid agents are reviewed, and the potential future clinical and research areas of application are indicated.
Anions↗
Primary lung cancer: biodistribution and dosimetry of two In-111-labeled monoclonal antibodies.
This study was undertaken to measure the biokinetics and organ dosimetry of indium-111-labeled monoclonal antibodies (MoAbs) with a whole-body gamma camera imaging technique. Twenty patients with primary lung cancer were studied with two different MoAb agents (anti-carcinoembryonic antigen ZCEO25 and antiadenocarcinoma LA20207). Imaging was performed at 1, 24, 72, and 144 hours after injection. Scintigraphic whole-body retention was verified by means of comparison with the results from in vitro counting of excreta. Organ retention was verified in an abdominal phantom. The MoAb cleared slowly from the heart and lungs, the brain and spleen showed no clearance, and the liver showed increased activity over the 6-day period. Dosimetry for ZCE025 showed a dose to the liver of 1.3 rad/mCi (0.36 mGy/MBq); heart, 1.5 rad/mCi (0.40 mGy/MBq); spleen, 1.1 rad/mCi (0.29 mGy/MBq); total body, 0.49 rad/mCi (0.13 mGy/MBq); and testes, 0.39 rad/mCi (0.11 mGy/MBq). The dosimetry for LA20207 was similar.
Adenocarcinoma↗
Left ventricular response to submaximal and maximal exercise in asymptomatic aortic regurgitation.
In patients with chronic aortic regurgitation the quantitative changes in loading conditions and left ventricular performance from rest to submaximal exercise have not been related to the magnitude of change observed from rest to maximal exercise. Changes in end-diastolic volume index, as a measure of preload, and measures of contractile performance (ejection fraction and the systolic blood pressure/end-systolic volume index ratio) were assessed at rest, submaximal and maximal supine bicycle exercise using radionuclide angiography in 74 patients with chronic moderate to severe aortic regurgitation. With exercise, end-diastolic volume index decreased in a stepwise manner from 166 +/- 47 to 152 +/- 41 to 143 +/- 41 ml/m2 at rest, submaximal and maximal exercise, respectively. For the entire group, these changes were not associated with a significant change in ejection fraction but were associated with stepwise increases in systolic blood pressure to end-systolic volume index ratio. However, when patients were divided into 3 subgroups based on an increase (group I), minimal change (group II) or a decrease (group III) in ejection fraction from rest to maximal exercise, stepwise increases in systolic blood pressure to end-systolic volume index were again observed in groups I and II but not in group III. These changes were significantly greater in group I than in group II at submaximal and maximal exercise levels. Differences in ejection fraction response and end-diastolic and end-systolic volumes with exercise in the 3 groups were evident at the submaximal exercise level.(ABSTRACT TRUNCATED AT 250 WORDS)
Aortic Valve Insufficiency↗
Scintigraphic criteria for the diagnosis of obstructive hepatobiliary diseases with Tc-99m IDA.
The purpose of this study is to define the scintigraphic parameters that reliably predict the presence of obstructive hepatobiliary diseases. Gallbladder and intestinal visualization times noted during cholescintigraphy with Tc-99m IDA were compared to functional and morphologic parameters for their ability to accurately diagnose biliary diseases. One hundred and twenty-five normal subjects and 127 patients with five different types of hepatobiliary diseases were studied. Bile pooling in segmental ducts with minimal prolongation of excretion t-1/2 was the feature most commonly seen in partial common bile duct obstruction, and biliary nonvisualization with marked prolongation of excretion t-1/2 was the primary feature of total obstruction. Sclerosing cholangitis showed band constrictions and beading along bile ducts with regional variation in excretion t-1/2, and primary biliary cirrhosis demonstrated normal bile ducts with uniform prolongation of excretion t-1/2. Patients with cholelithiasis showed normal image patterns of the major ducts. Intestinal visualization by 60 minutes was only 46% sensitive and 77% specific with an overall accuracy of 74% in the detection of biliary obstruction. Delayed gallbladder visualization and reduction in ejection fraction were sensitive but nonspecific indicators of biliary disease. We conclude that Tc-99m-IDA imaging is an accurate test for the diagnosis of obstructive hepatobiliary disease provided both quantitative functional and qualitative morphologic parameters are analyzed. Intestinal nonvisualization at 60 minutes alone is not reliable as a sole parameter for the detection of partial biliary obstruction.
Adult↗
Gallbladder filling and post-ceruletide emptying in prairie dogs and rabbits.
The filling and emptying characteristics of the gallbladder in prairie dogs and rabbits were studied to assess the importance of the residual bile in the pathogenesis of gallstones. In prairie dogs under ketamine/xylazine anesthesia, a significantly larger fraction (p = 0.001) of hepatic bile entered the gallbladder (87 +/- 8%) than the intestine during fasting and very little bile emptied (0-3% ejection fraction) following ceruletide infusion. In rabbits under similar anesthesia, only a small fraction of hepatic bile entered the gallbladder (4 +/- 2%) during fasting, and the gallbladder emptied almost completely (85% ejection fraction) following ceruletide infusion. The resultant higher residual bile in the prairie dog gallbladder and lower residual bile in the rabbit gallbladder may explain why gallstones form so readily in prairie dogs but not in rabbits when fed a lithogenic diet. These similarities and differences in gallbladder function must be taken into account when considering any animal as a model for gallstone formation.
Animals↗
Primary biliary cirrhosis: Tc-99m IDA planar and SPECT scanning.
The authors studied ten patients with primary biliary cirrhosis using planar and single photon emission computed tomography (SPECT); results were compared with those from 13 healthy subjects. Patients with primary biliary cirrhosis had six- to tenfold prolongation of mean halflife (t 1/2) hepatic excretion of technetium-99m iminodiacetic acid (IDA) compared with mean t 1/2 excretion in healthy subjects. All patients with primary biliary cirrhosis had diffuse, uniform hepatic isotope retention and normal major bile ducts on planar and SPECT scans. The gallbladder was seen within 60 minutes in nine of nine patients who had intact gallbladders. The mean gallbladder volume was normal, but gallbladder ejection fractions and ejection rates were reduced in patients with primary biliary cirrhosis compared with those of healthy subjects. In contrast with previous studies of patients with sclerosing cholangitis and common bile duct obstruction, patients with primary biliary cirrhosis had different findings on scintiscans. In the early evaluation of patients with cholestasis, Tc-99m IDA hepatobiliary scintigraphy may be useful in the selection of the most appropriate invasive diagnostic test to enable a definitive diagnosis.
Adult↗
Nuclear hepatology: where is it heading now?
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Humans↗