Joint Program in Nuclear Medicine

Nonvisualization of the Gallbladder at 1 Hour: Imaging Options

Jac D. Scheiner, MD 
J. Stevan Nagel, MD

October 31, 1995

Presentation

A 35 year old male presented with right upper quadrant pain and fever.

Imaging Technique

Imaging was performed after i.v. injection of 3 mCi Tc 99m - DISIDA. Using a low energy, parallel hole collimator, a 500,000 to 1,000,000 count initial image was obtained. Then, anterior images were obtained for the same amount of time every 5 minutes. After 1 hour Morphine Sulfate was administered i.v. in a dose of 0.04 milligrams / kg over 3 minutes.

Imaging Findings

Hepatobilliary scintigraphy shows prompt uptake into the liver and prompt excretion into the gastrointestinal tract. There is no visualization of the gallbladder within the first hour of imaging. After administration of Morphine Sulfate, there is visualization of the gallbladder (seen on the last line).

Discussion

At least 95% of cases of acute cholecystitis are due to an obstructed cystic duct (most often due to a stone, although viscous bile / debris may obstruct as well). Since hepatobiliary scintigraphy using an iminodiacetic acid (IDA) agent directly investigates cystic duct patency, it is the first study of choice (1). A retrospective study of 100 patients with pathology proven acute cholecystitis, who had both an ultrasound and hepatobiliary scintigraphy within 48 hours of each other, found the sensitivities of hepatobiliary scintigraphy using DISIDA, ultrasound using liberal criteria (stones, thick wall, Murphy sign), and strict criteria (thick wall, pericholecystic fluid) were 97%, 86%, and 24% respectively.

Iminodiacetic Acid Agents

Iminodiacetic acid agents act as 'bile analogs', except that they are not conjugated. DISIDA, which is 88% taken up by the liver, can be used effectively for bilirubin levels up to 20-30 mg/dl. The patient should not have eaten within 4 hours of the exam (a contracted gallbladder may not significantly fill with tracer), although the patient should have eaten within 24 hours of the exam (if the gallbladder is filled with bile, it may not fill with tracer). In these 'fasting patients', pretreatment with Sincalide (a cholecystokinin analog) is performed to empty a potentially bile and/or sludge filled gallbladder.

Normal Findings

A normal DISIDA scan will demonstrate prompt, homogeneous tracer uptake in the liver. The cardiac blood pool should no longer be seen by 5 to 10 minutes after injection. The common bile duct, gallbladder, and small intestine should be visualized at approximately 10 minutes, 14 minutes, and 22 minutes respectively(2). In about 19% of normal subjects, the small bowel will not be visualized until after 1 hour(2).

Abnormal Findings

An abnormal DISIDA scan in the evaluation of acute cholecystitis is one in which the gallbladder is not visualized. This is usually due to cystic duct obstruction by a stone, although an anatomically absent gallbladder (either surgically or congenitally), contracted gallbladder, gallbladder filled with stones, bile and/or sludge, poor hepatic function, or acalculus cystic duct obstruction may give a similar appearance(3).

Nonvisualization at 1 Hour

Nonvisualization of the gallbladder at 1 hour is one of the most common problems faced in hepatobiliary scintigraphy . The three options are available to the nuclear medicine physician:

Morphine Sulfate

Morphine Sulfate administration is used to contract the sphincter of Oddi, increasing pressure in the common bile duct, and facilitating reflux of tracer through the cystic duct, into the gallbladder. An i.v. dose of 0.04 milligrams / kg is given over 1-3 minutes. Imaging is then performed for an additional 30 minutes (sometimes with an additional, lower dose injection of tracer). The sensitivity of this study is typically greater than 95%, whereas the specificity has been reported to range from 69% to 100%, with the true specificity probably in the 85% - 90% range(4,5,6,7,8,9). False positive studies are usually due to chronic cholecystitis with fluid and / or stones in the gallbladder which prevent adequate filling. False negative studies are even rarer, although they have been reported in cases of 1) gallbladder perforation (in which the decrease in gallbladder luminal pressure allowed the obstructing cystic duct stone to dislodge, and tracer refluxed into a contained perforation)(10) and 2) acute gangrenous cholecystitis (the cystic duct was thickened and inflamed, although not enough to occlude its lumen)(11). Clues to a false negative exam would include a strange configuration to the 'gallbladder' in the former case, and a 'rim sign' in the latter case.

Sincalide

Sincalide administration is used to empty the gallbladder contents prior to the study, thus increasing the likelihood of tracer reflux into its lumen. An i.v. dose of 0.02 micrograms / kg is given in 30 ml normal saline and infused as a slow continuous dose over 15-30 minutes for maximal effectiveness. The drawbacks include having to wait 30 minutes before reimaging and the more complicated pharmacokinetics. In addition, a study in which 60 patients with nonvisualization of the gallbladder at 1 hr on DISIDA scans were given either Sincalide or MSO4 (30 cases in each group), showed that while both interventions had greater than 93% sensitivity, the MSO4 studies were much more specific for acute cholecystitis (100% vs. 84%)(12). Abnormal gallbladder wall innervation seen in cases of chronic cholecystitis may prevents adequate response to Sincalide, and thus their retained intraluminal contents will continue to inhibit tracer flow into the gallbladder.

Delayed Imaging

Delayed imaging is useful in that no further pharmacologic intervention is needed (with the exception of possible tracer reinjection). However, it may take up to 4 hours status post injection for the gallbladder to be visualized. Also, in a study comparing MSO4 and delayed imaging (at 3-24 hours) in 91 patients whose gallbladder was not visualized at 1 hour, both studies were over 91% sensitive, although the specificity of MSO4 was significantly greater than that of delayed imaging (79% vs 34%)(13). Of the 19 false positive cases on delayed imaging, 14 were due to chronic cholecystitis.

Summary:

Morphine Sulfate augmented hepatobiliary scans provide greater than 93% sensitivity in diagnosing acute cholecystitis, with a greater specificity than either Sincalide augmented imaging or delayed imaging. The dose administered is relatively safe, with the only contraindications being a known allergy, pancreatitis, or respiratory compromise. The most common cause of a false positive exam is chronic cholecystitis. If this is suspected initially, a Sincalide gallbladder ejection fraction study may be performed before Morphine Sulfate intervention (the biological t1/2 of Morphine Sulfate is approximately 3 hours(14), whereas the biological t1/2 of Sincalide is approximately 3 minutes(15)). False negative exams are rare, although they have been reported in cases of gallbladder perforation and gangrenous cholecystitis.

References

1. Fink-Bennet D, Freitas JE, Ripley SD and Bree RL. The Sensitivity of Hepatobiliary Imaging and Real-Time Ultrasonography in the Detection of Acute Cholecystitis. Arch Surg 1985;120:904-906.

2. Williams W, Krishnamurthy GT, Brar HS, and Bobba VR. Scintigraphic Variations of Normal Biliary Physiology. J Nucl Med 1984;25:160-165.

3. Datz FL. Gamuts in Nuclear Medicine, 2nd Ed. 1987; 222.

4. Choy D, Shi EC, McLean RG, Hoscho R, Murray IPC, Ham JM. Cholescintigraphy in acute cholecystitis: use of intravenous morphine. Radiology 1984;151:203- 207.

5. Keslar PJ, Turbiner EH. Hepatobiliary imaging and the use of intravenous morphine. Clin Nucl Med 1987;12:592-596.

6. Vasquez TE, Greenspan G, Evans DG, Halpern SE, Ashburn WL. Clinical efficacy of intravenous morphine administration in hepatobiliary imaging for acute cholecystitis. Clin Nucl Med 1988;13:4-6.

7. Flanbaum L, Alden SM. Morphine cholescintigraphy. Surg Gynecol Obstet 1990;171:227-232.

8. Fink-Bennet D, Balon H, Robins T, Tsai D. Morphine-augmented cholescintigraphy: its efficacy in detecting acute cholecystitis. J Nucl Med 1991;32:1231- 1233.

9. Fig LM, Wahl RL, Stewart RE, Shapiro B. Morphine- augmented hepatobiliary scintigraphy in the severely ill: caution is in order. Radiology 1990;175:467-473.

10. Achong DM, Newman JS and Oates E. False- negative morphine-augmented cholescintigraphy: a case of subacute gallbladder perforation. J Nucl Med 1992;33:256-257.

11. Yeo EE, Low JC, and Azizi F. False-negative morphine-augmented cholescintigraphy in a patient with gangrenous cholecystitis. Clin Nucl Med 1992;17:929-930.

12. Yen TC, King KL, Chang SL, and Yeh SH. Morphine - augmented vs CCK - augmented cholescintigraphy in diagnosing acute cholecystitis. Nucl Med Comm 1995;16:84-87.

13. Kim CK, Tse KKM, Juweid M, Mozley PD, Woda A and Alavi A. Cholescintigraphy in the Diagnosis of Acute Cholecystitis: Morphine Augmented is Superior to Delayed Imaging. J Nucl Med 1993;34:1866-1870.

14. Gilman AG, Goodman LS, Rall TW and Murad F. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 7th Ed. 1985; 505.

15. Thomas JC, Fender HR, Rawus NI, et al. Cholecystokinin metabolism in man and dogs. Ann Surg 1975;182:496.

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J. Anthony Parker, MD PhD, Tony_Parker@bidmc.harvard.edu