Extended application of 99mTc-mebrofenin cholescintigraphy with cholecystokinin in the evaluation of abdominal pain of hepatobiliary and gastrointestinal origin.

OBJECTIVE: To explore the extension of cholecystokinin-cholescintigraphy in the evaluation of abdominal pain. METHODS: A total of 1554 patients with abdominal pain underwent Tc-mebrofinin cholescintigraphy. Gallbladder ejection fraction was obtained with cholecystokinin (sincalide) and abdominal pain was graded. RESULTS: Fourteen different types of hepatobiliary and gastrointestinal motility disorders were identified. Biliary dyskinesia was found in 453 patients, septate gallbladder in 33, and duodeno-gastric bile reflux in 46 patients. Sincalide-induced intestinal hyperperistalsis alone was found in 65 and in combination with other diseases in 64 patients. Abdominal pain was mild to moderate in intensity, and occurred in 50-60% of patients with abnormal gallbladder function. Severe abdominal pain was usually associated with intestinal hyperperistalsis. CONCLUSION: Tc-mebrofinin cholescintigraphy enables the identification of motility disorders of the gastrointestinal and hepatobiliary tract, and post-sincalide abdominal pain in most cases can be assigned to functional abnormality of the gallbladder or/and intestine.

Development and validation of a comprehensive new hepatobiliary software. Part II: Segmental liver function.

OBJECTIVE: This study was undertaken to develop comprehensive new hepatobiliary software to quantify segmental and lobar liver function and to obtain FDA approval. METHODS: Hepatobiliary software written on JAVA platform and loaded on to a PC accepts 99mTc-HIDA dicom image data transferred from a gamma camera. Liver boundary was determined by threshold-based auto edge detection and liver height at right midclavicular (RMCL) line. Geometric mean area of the physiologic right lobe, physiologic left lobe and total liver area were measured. Segmental liver function was determined using the 5th minute frame as the default (100%). RESULTS: In 24 control participants, mean (+/-SD) liver height at RMCL was 14.7+/-0.12 cm. Geometric mean area of the physiologic right lobe was 116+/-3 cm2, left lobe 96+/-4 cm2, and total liver area 212+/-3 cm. Right upper lobe (segments 7 and 8) contributed 31+/-0.7%, right lower lobe (segments 5 and 6) 34+/-0.6%, left medial (segments 4A and 4B) 24+/-1%, left lateral (segments 2 and 3) 10+/-2%, and caudate lobe (segment 1) 1+/-0.02% of total liver function. In 23 patients, contrast three-dimensional computerized tomographic volume of the right lobe was 1194+/-419 ml, left lobe 434+/-221 ml, and total liver volume 1628+/-490 ml. Right lobe area was 120+/-30 cm2, left lobe (plus caudate) 88+/-29 cm2 with total liver area of 208+/-51 cm. Right upper lobe (segments 7 and 8) contributed 33+/-10%, right lower lobe (segments 5 and 6) 34+/-7%, left medial (segments 4A and 4B) 23+/-6%, left lateral (segments 2 and 3) 9+/-3%, and caudate lobe (segment 1) 1+/-0.4% of total liver function. There was good correlation of RMCL height, and area of right lobe and total liver with computerized tomographic liver volume. Correlation of percentage volume with percentage function was excellent. CONCLUSION: New FDA approved software provides quantitative assessment of segmental, lobar, and total liver size and function from a planar 99mTc-HIDA cholescintigraphy and may enable universal standardization in nuclear hepatology. Quantification may aid surgeons in the determination of the amount of tissue resection during liver surgery.

Development and intra-institutional and inter-institutional validation of a comprehensive new hepatobiliary software: Part 1--Liver and gallbladder function.

OBJECTIVE: To develop a software tool for quantification of liver and gallbladder function, and to assess the repeatability and reproducibility of measurements made with it. MATERIALS AND METHODS: The software tool developed with the JAVA programming language uses the JAVA2 Standard Edition framework. After manual selection of the regions of interest on a 99mTc hepatic iminodiacetic acid study, the program calculates differential hepatic bile flow, basal duodeno-gastric bile reflux (B-DGBR), hepatic extraction fraction (HEF) of both the lobes with deconvolutional analysis and excretion half-time with nonlinear least squares fit. Gallbladder ejection fraction, ejection period (EP), ejection rate (ER), and postcholecystokinin (CCK) DGBR are calculated after stimulation with CCK-8. To assess intra-observer repeatability and intra-observer reproducibility, measurements from 10 normal participants were analyzed twice by three nuclear medicine technologists at the primary center. To assess inter-site reproducibility, measurements from a superset of 24 normal participants were also assessed once by three observers at the primary center and single observer at three other sites. RESULTS: For the 24 control participants, mean+/-SD of hepatic bile flow into gallbladder was 63.87+/-28.7%, HEF of the right lobe 100+/-0%, left lobe 99.43+2.63%, excretion half-time of the right lobe 21.50+6.98 min, left lobe 28.3+/-11.3 min. Basal DGBR was 1.2+/-1.0%. Gallbladder ejection fraction was 80+/-11%, EP 15.0+/-3.0 min, ER 5.8+/-1.6%/min, and DGBR-CCK 1.3+/-2.3%. Left and right lobe HEF was virtually identical across readers. All measures showed high repeatability except for gallbladder bile flow, basal DGBR, and EP, which exhibited marginal repeatability. Ejection fraction exhibited high reproducibility. There was high concordance among the three primary center observers except for basal DGBR, EP, and ER. Concordance between the primary site and one of the other sites was high, one was fair, and one was poor. CONCLUSION: New United States Food and Drug Administration-approved personal computer-based Krishnamurthy Hepato-Biliary Software for quantification of the liver and gallbladder function shows promise for consistently repeatable and reproducible results both within and between institutions, and may help to promote universal standardization of data acquisition and analysis in nuclear hepatology.

Segmentation of the gallbladder: effect on bile entry and exit and its clinical relevance in a patient with abdominal pain.

BACKGROUND: The effects of folds or septa on gallbladder filling and emptying are not known. METHODS: Gallbladder filling and emptying were measured in seven patients with two chambers (segmental) and compared with 10 subjects with a single chamber (control). Percent bile flow into gallbladder, and percent ejection fraction from the proximal and distal segments, and entire gallbladder were measured with cholecystokinin. RESULTS: Bile entry into gallbladder was similar in both groups. In patients with segmentation, overall emptying was low mostly due to poor emptying of the distal segment. CONCLUSION: Segmentation of the gallbladder does not affect bile entry, but acting as a one-way valve, a fold or septum lowers emptying significantly, mostly from the distal segment.

Effect of sequential administration of an opioid and cholecystokinin on gallbladder ejection fraction: brief communication.

UNLABELLED: This study was undertaken to test the effect of sequential administration of an opioid and intravenous cholecystokinin (CCK) on gallbladder ejection fraction. METHODS: Forty-nine patients who had received an opioid underwent quantitative cholescintigraphy with octapeptide of CCK (CCK-8). Gallbladder ejection fraction and CCK-8-induced paradoxical filling were calculated. RESULTS: In the basal state, more of the hepatic bile entered the gallbladder (67%) than the small intestine (33%). After CCK-8 infusion, gallbladder ejection fraction was low in 37 (76%) of 49 patients and normal in 12 (24%). All 5 types of opioids lowered ejection fraction. CCK-induced paradoxical filling of the gallbladder was noted in 7 patients, but only one showed paradoxical filling of greater than 20% and none had a normal gallbladder ejection fraction. The lowering effect of opioids on gallbladder ejection fraction may last as long as 18 h after intake. CONCLUSION: CCK-8 produced a normal gallbladder ejection fraction in 24% of patients who had received an opioid and thus could exclude both acute and chronic cholecystitis during a single hepatobiliary study.

Constancy and variability of gallbladder ejection fraction: impact on diagnosis and therapy.

UNLABELLED: The main objective of this study was to test the constancy and variability of gallbladder (GB) ejection fraction (EF) in long-term studies to (a) determine whether EF ever becomes normal once it is low, (b) determine how long it takes for the EF to become abnormal once it is found to be normal, (c) explore the cause of low EF, and (d) define objective parameters for biliary and nonbiliary abdominal pain. METHODS: Fifty-two patients (42 women, 10 men) who underwent quantitative cholescintigraphy twice (total studies, 104), over a mean period of 38.54 mo between studies, were chosen for retrospective analysis. They were divided into the following groups: control (n = 13; nonbiliary abdominal pain), chronic acalculous cholecystitis (CAC) (n = 27; biliary abdominal pain), chronic calculous cholecystitis (CCC) (n = 6; biliary abdominal pain), and opioid (n = 6; nonbiliary abdominal pain). The last group had received an opioid before cholecystokinin-8 (CCK-8) infusion in one study but not in the other study. A GBEF value of > or =35% was considered normal with a 3-min infusion and > or =50% as normal with a 10-min infusion of CCK-8. RESULTS: The mean GBEF value was reproducible between the 2 sequential studies in the control group (66.0% +/- 20.5% vs. 73.9% +/- 17.7%), CAC group (24.4% +/- 22.3% vs. 16.9% +/- 10.9%), and CCC group (20.8% +/- 20.9% vs. 27.5% +/- 34.5%) but not in the opioid group (14.8% +/- 14.6% vs. 56.5% +/- 31.7%). The severity of GBEF reduction in CAC increased with time: 7.2% +/- 8.1% within 12 mo, 16.1% +/- 14.9% in 13-47 mo, and 23.5% +/- 21.3% in 48-168 mo. None of the 27 patients with CAC developed a gallstone as detected by ultrasound during the study period. In 5 patients with CAC, a mean period of 52.6 +/- 28.9 mo was required for conversion from normal to a low EF. CCK-induced cystic duct spasm is the etiology for low EF in both CAC and CCC. CONCLUSION: Normal and low GBEF values are reproducible in long-term studies. Once the EF reaches a low value, it does not return to normal, and a normal value requires many years to become abnormal. CCK-induced cystic duct spasm is the cause of low GBEF in CAC and CCC, and the severity of EF reduction is similar for both. Exclusion of opioid intake immediately before the study is critical before attributing a low GBEF value to an irreversible GB motor dysfunction.

Characterization of basal hepatic bile flow and the effects of intravenous cholecystokinin on the liver, sphincter, and gallbladder in patients with sphincter of Oddi spasm.

The major objectives of this project were to establish the pattern of basal hepatic bile flow and the effects of intravenous administration of cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight women with clinically suspected sphincter of Oddi spasm (SOS group), ten control subjects (control group), and ten patients who had recently received an opioid (opioid group) were selected for quantitative cholescintigraphy with cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium-99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60 min, followed by gallbladder phase images for 30 min. During the gallbladder phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min through an infusion pump. Hepatic extraction fraction, excretion half-time, basal hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post-CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the patients with SOS were treated with antispasmodics (calcium channel blockers), and one underwent endoscopic sphincterotomy. Mean (+/-SD) hepatic bile entry into the gallbladder (versus GI tract) was widely variable: it was lower in SOS patients (32%+/-31%) than in controls (61%+/-36%) and the opioid group (61%+/-25%), but the difference was not statistically significant. Hepatic extraction fraction, excretion half-time, and pattern of bile flow through both intrahepatic and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection fraction was 9%+/-4% in the opioid group; this was significantly lower (P<0.0001) than the values in the control group (54%+/-18%) and the SOS group (48%+/-29%). Almost all of the bile emptied from the gallbladder refluxed into intrahepatic ducts; it reentered the gallbladder after cessation of CCK-8 infusion (paradoxical gallbladder filling) in all eight patients with SOS, but in none of the patients in the other two groups. Mean paradoxical filling was 204% (+/-193%) in the SOS group and less than 5% (P<0.05) in both the control and the opioid group. After treatment, six of the SOS patients had complete pain relief and one, partial pain relief. The basal tonus of the sphincter is variable in patients with SOS, and allows relatively more of the hepatic bile to enter the GI tract than the gallbladder. Due to simultaneous contraction of the sphincter and gallbladder in response to CCK-8, most of the bile emptied from the gallbladder refluxes into intrahepatic ducts, and reenters the gallbladder immediately after cessation of hormone infusion. The characteristic features of gallbladder filling, emptying, and paradoxical refilling with cholecystokinin provide objective parameters for noninvasive diagnosis of SOS by quantitative cholescintigraphy.

Comparison of gallbladder function obtained with regular CCK-8 and pharmacy-compounded CCK-8.

UNLABELLED: This study was undertaken to test whether the octapeptide of cholecystokinin (regular CCK-8) and pharmacy-compounded CCK-8 produce similar results with regard to gallbladder function. METHODS: Twenty patients with suspected gallbladder disease were enrolled into quantitative cholescintigraphy. Each patient was infused for 10 min with 3 ng/kg/min of regular CCK-8 and pharmacy-compounded CCK-8, sequentially, with a 30-min interval between the beginning of infusion. The gallbladder ejection fraction, latent period, ejection period, and ejection rate were measured with both agents. RESULTS: Both regular CCK-8 and pharmacy-compounded CCK-8 produce similar, but not identical, results with close correlation between them with reference to all of the measured functions of the gallbladder. There is neither potentiation nor inhibition of the first dose on the effects of the second dose of CCK-8. CONCLUSION: Pharmacy-compounded CCK-8 functions much similar to that of regular CCK-8 as long as an interval of at least 30 min is allowed between doses.

Comparison of fatty meal and intravenous cholecystokinin infusion for gallbladder ejection fraction.

UNLABELLED: Gallbladder ejection fraction (GBEF) measured with a fatty meal (half-and-half milk) was compared with that measured with 2 equal sequential intravenous infusions of cholecystokinin (CCK-8) in a paired study of healthy subjects. METHODS: GBEF was measured by (99m)Tc-hepatic iminodiacetic acid cholescintigraphy in 13 healthy subjects. Each subject received 2 sequential doses of CCK-8 (3 ng/kg/min for 10 min) on day 1, followed by, on day 2, a 240-mL (8 oz) fatty meal (half-and-half milk) per 70 kg of body weight. RESULTS: The mean +/- SD GBEF of 53.6% +/- 20.2% with fatty meal was significantly lower than the mean of 75.8% +/- 16.3% (P < 0.01) with the first dose of CCK-8 and 71.3% +/- 17.4% (P < 0.05) with the second dose. Fatty meal GBEF varied widely, from 23.5% to 91.8%. Percentile rankings of the fatty meal GBEF were determined as the preferred methodology for reporting results. Latent and ejection periods were significantly longer with fatty meal than with either dose of CCK-8. CONCLUSION: GBEF measured with fatty meal can serve as an alternative method to intravenous injection of CCK-8 when the hormone is no longer available for clinical use. The measurement of GBEF with fatty meal requires careful attention to the details of the meal and the measurement time sequence.

Hepatic bile entry into and transit pattern within the gallbladder lumen: a new quantitative cholescintigraphic technique for measurement of its concentration function.

UNLABELLED: The aim of the project was to study hepatic bile entry into and the transit pattern within the gallbladder lumen during fasting and to introduce a new quantitative scintigraphic test for measurement of its concentration function. METHODS: Each of 10 control subjects and 10 chronic acalculous cholecystitis (CAC) patients received 111-185 MBq 99mTc-mebrofenin as a hepatic bile marker. Gamma-camera image data were collected in the anterior view on a 128 x 128 x 16 computer matrix at 1 frame per minute for 60 min for the hepatic phase and 30 min for the gallbladder phase. The radiolabeled hepatic bile area within the gallbladder lumen was traced, and the net transit area and transit time were noted. The hepatic bile transit rate was calculated (as mm2/min) and normalized to 1,000 mm2 of the anterior gallbladder area. The cholecystokinin-8-induced ejection fraction was calculated nongeometrically using counts. RESULTS: Hepatic bile entered the gallbladder continuously during fasting with a mean +/- SD of 71% +/- 20% in control subjects and 59% +/- 27% in CAC patients, which were not significantly different (P > 0.05). The maximum frontal gallbladder area was 1,699 mm2 in control subjects and 1,610 mm2 in CAC patients (P > 0.05). Radiolabeled hepatic bile entered the gallbladder first along its central long axis in both groups, at a mean of 15 min and 16 min, respectively, and traveled toward the periphery in a lamellar fashion at a normalized mean rate of 38 mm2/min and 40 mm2/min in control subjects and CAC patients, respectively. The mean ejection fraction of 17% in CAC patients was significantly lower than the mean value of 56% in control patients (P < 0.00001). CONCLUSION: Hepatic bile enters the gallbladder continuously during fasting. In patients with CAC, the gallbladder maintains the normal concentration function but the contraction and emptying are reduced significantly. This new cholescintigraphic technique enables measurement of both functions sequentially with a single dose of 99mTc-mebrofenin.