Technetium-99m BIDA Biliary Scintigraphy in the Evaluation of the Jaundiced Patient

Anthony W. Lee, Madhira D. Ram, Wei-Jen Shih, and Karen Murphy

Surgical and Nuclear Medicine Services, V. A. Medical Center and the Department of Surgery, University ofKentucky Medical Center, Lexington, Kentucky

Biliary scintigraphy using @“Tcp-butyl acetanilidiminodiacetic acid (BIDA) was performed as partof the diagnosticevaluationon 96 patientswith jaundice(serumbilirubin>2 mg/dl)to assessits valuein this groupof patients.Theresultsof scintigraphyrevealed(a)no obstruction to the flow of the scintigraphic agent into the duodenum in 54 patients, (b) delayed appearance of the agent (normal upper limit 60 mm) in the duodenum indicating partial obstruction in 22 patients, and (c) complete obstruction of the duct demonstrated by absenceof agentin the duodenumin 20 patients.Thefindingswerecorrelatedwith the final diagnosisandthe overallresultsshowaccuracyof 92.7%,sensitivityof 97.3%,and specificityof 89.8%.Biliaryscintigraphywas thusfoundto be usefulin differentiating nonobstructive,partiallyobstructive,andcompletelyobstructivecausesof jaundice.

J Nucl Med 27:1407—1412,1986

he differentiation ofjaundice due to the hepatocel the diagnostic value of scintiscanning in jaundiced pa lular disease (medical jaundice) from extrahepatic bili tients (5—7).Klingensmith et al. stated that US and ary obstruction (surgical jaundice) is important in plan hepatobiliary scintigraphy have a complementary role fling the appropriate diagnostic and therapeutic in the evaluation ofbiliary obstruction (8). Their group procedures. also suggested that intrahepatic cholestasis can be di Currently, there are a number of radiologic tech agnosed by hepatobiliary scintigraphy (9). This study niques available in the investigation of a jaundiced reviews our experience with the use of radionuclide patient. These include: ultrasonography (US), corn hepatobiliary imaging as a screening procedure in puted tomography (CT), percutaneous transhepatic jaundiced patients. cholangiography (PTC), and endoscopic retrograde cholangio-pancreatography (ERCP) ( 1). Some of these (PTC and ERCP) are invasive and/or expensive. Fur MATERIALS AND METHODS thermore, they delineate anatomic lesions but do not provide a functional evaluation. On the other hand, During the period March 1, 1979, through April 30, radionuclide hepatobiliary scanning is a noninvasive 1983, we studied 96 patients who were clinically jaun study and provides the only means of functional diced. All patients were from our institution and in evaluation along with imaging. cluded 79 males and 17 females. The age range was 1 In selecting a single screening test which can differ mo to 92 yr (mean 52 yr). entiate medical from surgical causes of jaundice, one The levels of serum bilirubin ranged from 2.1—38.8 has to take into account ease of performance, cost mg/dl (normal 0. 1—1.1 mg/dl). Excluded from this effectiveness, complications associated with the proce review were patients who carried a diagnosis of either dure, and degree of accuracy. With the introduction of acute or chronic cholecystitis alone and also patients newer radiopharrnaceuticals such as p-butyl acetanilid who have had previous biliary enteric bypass. These iminodiacetic acid (BIDA) labeled with technetium have been previously reviewed by one of us (2—4,10). 99m (99mTc) interest in hepatobiliary scintiscanning In addition to scintiscanning, all patients underwent has increased (2—4). clinical, chemical, radiologic, and endoscopic evalua There has not been uniform agreement concerning tions as required. The final diagnosis in each patient

Received July 19, 1985; revision accepted Mar. 6, 1986. was based on the results of all studies noted above and For reprints contact: M.D. Ram, MD, PhD, Chief, Surgical additionally in most patients based on operative find Service, V. A. Medical Center, Lexington, KY 405 11. ings or needle biopsy of the liver (details in results).

Volume27 •Number9 •September1986 1407 Informed consent was obtained from all subjects. There are two scintigraphic patterns of complete Technetium-99m BIDA was used as scanning agent obstruction of the common bile duct. One is that of a and was prepared from a commercial kit and 5mCi of fairly rapid hepatic uptake of the tracer by the liver but [99mTc]BIDA was injected intravenously. Using a no visualization ofthe hepatic ducts, the common duct, gamma camera,t images were obtained at 2, 5, 10, 15, gallbladder, or the bowel even up to 24 hr after injection 30, 45, and 60 mm after the injection and then at 15- (13,14) (Fig. 2). The other pattern is a hyperacute mm intervals for up to 90 to 120 mm. Further scans complete common bile duct obstruction, scintigraphic were obtained at 4 to 6 hr as needed and up to 24 hr if features ofwhich include rapid uptake and visualization indicated. Each image accumulated 300—500kcounts. of the hepatic ducts, common bile duct, and the gall The details of this technique were previously described bladder, but no appearance of activity in the bowel (2,11). through the 24-hr study period (15) (Fig. 4). Only one patient in the study showed this pattern. The results of scintigraphy were correlated with the RESULTS final diagnosis (Tables 1, 2, and 3). The following defi In a normal scintigram, the liver is visualized at 5 to nitions were used: (a) true negative—no obstruction or 10 mm after injection of the agent, the gallbladder at delay of agent into the duodenum in the scan and no

,@‘1 5—20 mm and complete images ofthe liver, galiblad obstruction demonstrated, (b) true positive—obstruc der, common bile duct, and proximal small bowel are tion or delay of agent into the duodenum by scan and obtained between 25 and 30 mm. The criteria used to obstruction confirmed, (c) false positive—obstruction define extrahepatic biliary obstruction are based on or delay of agent into the duodenum by scan but no whether the gallbladder and the common bile duct were obstruction present, and (d) false negative—no obstruc visualized or not and whether there is radionuclide tion or delay of agent into the duodenum by scan but activity in bowel or not and also the time of appearance obstruction present. of this activity. Based on the above, the sensitivity of the scan was The results of scintigraphy in this group were classi 97.3%, the specificity was 89.8%, and the overall fled into three categories as follows: (a) nonobstructive accuracy was 92.7%. group (no obstruction to the flow of the scintigraphic agent into the duodenum), 54 patients; (b) partially DISCUSSION obstructive (partial obstruction on the basis of delayed appearance of the agent: 60 mm or more in the bowel), Our results suggest that scintigraphy is useful in the 22 patients (Fig. 1); and (c) completely obstructive initial evaluation of the jaundiced patient. The differ (absence of the scanning agent in the small bowel even entiation of obstructive from nonobstructive jaundice after 24 hr), 20 patients (Fig. 2). has been a subject of several conflicting reports (17— In eight patients who were categorized as partial 20). The area of greatest difficulty centers around the obstruction, in addition to delayed radioactive tracer fact that at very high levels of serum bilirubin, lack of excretion in bowel, there was a scintigraphic pattern of images may be due to hepatocellular disease (poor intrahepatic bile pooling along the area and/or segmen hepatic uptake) or extrahepatic biliary obstruction tal defect in common bile duct (Fig. 3). This character (poor excretion) ( 16,21). In the former situation the istic pattern has been previously documented (12). tracer remains in the blood pool for a long time and

FIGURE 1 Partial obstruction of common bile duct: Fairly rapid radiotracer hepatic uptake and no visualizationof bile ducts, gallbladder,and bowel in 5-, 10-, 15-, 30-, and 60-mm images; colonicactivityseenin 24-hrimages but substantial radiotracer remaining I in liver at 24 hr, indicatingsevere partialobstruction ii. 24k

1408 Lee, Ram, Shih et al The Journal of Nuclear Medicine 15m 30m 2h

FIGURE 2 Complete obstruction due to biliary atresia in 2-mo-old girl: Radiotracer israpidlytakenbyliverbut bileducts, gallbladder,and bowel are persist ently not visualized, even in 20-hr 20h image the biliary tract will not be imaged. However, in patients tion has scintigraphic features that include rapid hepatic with very high levels of bilirubin, these results may be uptake and visualization of the hepatic ducts, the com equivocal because of dilution of the tracer ( 17). mon bile duct, and the gallbladder, but no appearance The scintigraphic patterns associated with biliary of activity in the bowel through and up to the 24-hr obstruction and jaundice are briefly outlined below. study period ( 15) (Fig. 4). This pattern is very rare 1. In complete obstruction ofthe common bile duct, because such a patient is usually studied immediately there is a fairly rapid hepatic uptake of the tracer, but following the onset of the common duct obstruction no visualization ofthe hepatic ducts, the common duct, while the gallbladder is still continuing to reabsorb gallbladder, or the bowel 24 hr after injection (13) water. There is an initial imaging of the biliary system (Fig. 1). while there is net bile flow until the bile is maximally 2. Hyperacute complete common bile duct obstruc concentrated. Eventually when the pressure in the sys

‘mom-@i@m‘@30m-@.@,@45@60m120m

FIGURE 3 Partial obstruction associated wfth intrahepaticbilepoolingandnarrow ingin commonbileduct: Bilepooling seen in 15-, 30-, 45-, and 60-mm images;abruptlynarrowingcommon duct seen in 30-, 45-, and 60-mm images

Volume27 •Number9 •September1986 1409 TABLE 1 NonobstructiveGroupby Scan AverageFinal clinical of bilirubin of diagnosisAlcOhOliCdiagnosisNo. patientsS. (mg/dl)Confirmation 2m 5m lOm biopsyAlcoholiccirrhosis127.1Liver biopsyUverhepatitis77.7Liver biopsyDrugmetastasis85.1Liver biopsylestasisSepsis41inducedcho 48.5Liver

0.4Exploratory celi otomyHepatitis41 15m 30m 45m 2.6Elevated hepatitis B, surface anti genLiver failure45.9HistoryNeonatal biopsySarcoidosis13.6Liverhepatitis29.1Uver biopsyChronic •1 biopsycongestionCirrhosis13.0Liverpassive11 3.5Liver Ih 3.5 h 24 h biopsyHodgkin's biopsyCytomegalovirusdisease16.8Liver FIGURE 4 biopsyfectionInfectedin 11 4.3Liver Hyperacutecompletecommonbileductobstruction:Rapid hepatic tracer uptake, in 30-mm to 24-hr images and aneurysm16.5Exploratory celi visualizationof gallbladder; no bowel activity seen through otomySubphrenic out studyupto 24 hr abscess12.8Exploratory celi otomyHepatoma11 1.0Operation and bi tem is high, net bile flow will cease and the scintigraphic opsyCholedocholithiasis13.4Ultrasonography pattern of complete common duct obstruction will operationTotal54. and result(14—16). 3. The pattern that is seen in patients with biliary atresia includes a delayed hepatic uptake with no vis ualization of hepatic ducts, common bile duct and bowel throughout the 24-hr period. In those patients False negative. who have been pretreated with phenobarbital, this pat tern is highly reliable for a diagnosis of biliary atresia labeled derivatives of iminodiacetic acid such as and separates this group from those with neonatal hep dimethylacetanilidiminodiacetic acid (HIDA) and atitis in whom gstrointestinal excretion is evident (21). p-butylacetanilidiminodiacetic acid (BIDA). From past 4. In intrahepatic cholestasis, there is a rapid hepatic experience, we have noted that using [99mTc]HIDA,we uptake and delayed appearance of activity in the bowel cannot accurately evaluate patients with serum biliru precluding a complete obstruction ofthe common duct. bin levels above 6 mg/dl whereas [99mTc]BIDAcan be Since the hepatic function is intact, the scintigraphic used even with serum bilirubin levels >30 mg/dl (2). pattern is similar to that due to partial obstruction of Technetium-99m BIDA was used as an investiga the excretory mechanism (21,22). In our study, there tional drug in this study and has the advantage that were two patients with drug induced cholestasis who more than 95% of this compound is excreted through fall into the partially obstructive group and were mis the bile (23). BIDA is protein bound and this high diagnosed. One other patient with alcoholic hepatitis protein binding and hepatic excretion is similar to the and a serum bilirubin of 20.5 mg/dl was also misdi manner in which rose bengal is handled by the liver. agnosed as “partiallyobstructive,― probably on the basis The amount of renal excretion of BIDA is <5% and is of the impaired uptake by the hepatocytes. not affected by hepatic function. Other IDA derivatives 5. Hepatic failure. In this group of patients, there is have a renal excretion in the range of 10—20%of a severely decreased hepatic uptake and persistently administered dose (24). However, in patients with he high cardiac or blood-pool activity with poor or even patic dysfunction, the proportion of renal excretion nonvisualization of the hepatic ducts, common bile increases and the more severe the hepatic dysfunction, duct, and the bowel. It is virtually impossible to differ the greater the degree ofrenal excretion (25). The higher entiate this condition from partially obstructed or renal excretion further impairs hepatobiliary scanning completely obstructed groups (13). and imaging because of the overlap of shadows and Interest in scintigraphy was revived in the mid 1970s effect ofthe blood pool. with the introduction of new agents which are 99mTc@ Our study yielded a sensitivity of 97.3%. There was

1410 Lee,Ram,Shihet al TheJournalof NuclearMedicine TABLE2 Partially Obstructive Group S. of bilirubin diagnosisCholedocholithiasis96.7OperationFinalclinicaldiagnosisNo. patientsAverage (mg/dl)Confirmation of cholangiogramPancreatitis33.1Laboratory and (amylase)andul trasonographyCommon cholangiogramPseudocyst—pancreas16.4Ultrasonographybileduct stricture212.2Operation and andbarium studiesCarcinoma—gallbladderI19.5Operation biopsyLeiomyosarcoma—stomach and biopsyductDrug displacing commonI5.6Operation and biopsySepsis•12.2History,inducedcholestasi&28.1Liver exploratorycell otomyGas culturesAlcoholicgangreneabdominalwai112.4Physical findings, biopsyTotal22.hepatiti&120.59Uver

False positive. only one false negative (2.7%). The patient had a mildly would be subjected to further diagnostic workup, elevated bilirubin with choledocholithiasis and may whereas 90% would be treated medically after the scan very well not have had enough extrahepatic obstruction results. In the “obstructive―group (surgical jaundice), to cause a delay in appearance of the agent into the all but one patient would have had further appropriate duodenum. Our false positives consist of six patients diagnostic studies before their operation. Scintigraphy, (5.76%). These patients had serum bilirubin in the therefore, is clearly of benefit as an initial screening range of 8.0—20.6 mg/dl. The dilution of tracer by procedure. It has the advantages of being noninvasive retained bile may have caused the delay in imaging of and it can provide a functional evaluation of the hepa the agent into the duodenum ( 17). tobiliary system in patients with elevated serum biliru By performing a BIDA scan as the initial procedure bin. It also has the advantages over ultrasonography in in the workup ofjaundiced patients, only 10% of the these patients because dilated loops of bowel do not “nonobstructive―group (medical jaundice) of patients interfere with the imaging. As with other noninvasive studies it is not completely infallible. A precise anatomic diagnosis is not feasible TABLE3 CompletelyObstructiveGroup with scintigraphy. In equivocal cases, clinical features and appropriate use of other studies, both invasive and S. Finalclinical of bilirubin of noninvasive, become important. diagnosisCarcinomadiagnosisNo. patientsAverage(mg/dl)Confirmation We feel that with a level ofaccuracy over 90%,biliary scintigraphy warrants serious consideration as a screen of pancreas81 5.5Operation and biopsyBiliary ing test because it offers a safe, simple procedure free andpatic)operationCommonatresia(extrahe 79.4Uver biopsy from complications, for primary evaluation of jaundiced patients. 16.7OperationtureCommonbileductstric In conclusion, biliary scintigraphy is useful as an initial screening tool in differentiating jaundiced pa 12.4OperationnosisIntra-abdominalbile duct ste tients into nonobstructive, partially obstructive and mass13.8Operationobstructing completely obstructive groups. commonbile ductHemOrrhagiC FOOTNOTES 115.3OperationtisPrimarypancreati . CIS-Us, Inc., Lake Success, NY. biopsyTotal20.biliarycirrhosis'113.0Liver t Siemens or General Electric.

REFERENCES 1. Toombs BD, Sandier CM: Medical versus surgical jaundice: When and how the radiologist can help. Tex False positive. Med77:52—58, 1981

Volume 27 •Number 9 •September 1986 1411 2. Ram MD, Hagihara PF, Kim EE, et al: Evaluation of 99m DISIDA. Clin Nucl Med 10:742—745,1985 biliary disease by scintigraphy. Am J Surg 141:77—83, 14. Klingensmith WC, Whitney WP, Spitzer VM, et al: 1981 Effect of complete biliary tract obstruction on serial 3. Ram MD, Mattingly SS, Kim EE, et al: Biliary scm hepatobiliary imaging in an experimental model: Con tiscanning in acute cholecystitis. World J Surg 6: 110— cisc communication. J NuclMed 22:866—868,1981 114,1982 15. Blue PW: Hyperacute complete common bile duct 4. Ram MD: The value of scintigraphy in the diagnosis obstruction demonstrated with Tc-99m IDA chole of biliary disease. Ann R Coil Surg Eng 63:333—336, scintigraphy. Nuc! Med Commun 6:275—279,1985 1981 16. Floyd JL, Collins TL: Discordance of sonography and 5. Matzen P, Malchow-Moller A, Brun B, et al: Ultra cholescintigraphy in acute biliary obstruction. Radio!- sonography, computed tomography, and cholescintig ogy 140:501—502,1983 raphy in suspected obstructive jaundice—A prospec 17. Taavisainen M, Korhola 0, Riihimaki E, et al: Tech tive comparative study. Gastroenterology 84:1492— netium-99m-diethyl-IDA cholescintigraphy in the dif 1497,1983 ferential diagnosis ofjaundice. Scand J Gastroentero! 6. O'Connor KW, Snodgrass PJ, Swonder JE, et al: A 14:567—575,1979 blinded prospective study comparing four current 18. Rosenthall L, Shaffer EA, Lisbona R, et al: Diagnosis noninvasive approaches in the differential diagnosis ofhepatobiliary disease by 99mTc-HIDA cholescintig of medical versus surgicaljaundice. Gastroenierology raphy. Radiology 126:467—474,1978 84:1498—1504,1983 19. Scott BB, Evans JA, Unsworth J: The initial investi 7. Zeman RK, Burrell MI, Gold JA, et al: The intrahe gation of jaundice in a district general hospital: A patic and extrahepatic bile ducts in surgical jaundice: study of ultrasonography and hepatobiliary scintigra Radiological evaluation and therapeutic implications. phy.BrJRadiol53:557—562,1980 CRC Cr11Rev DiagImaging21:1—36,1984 20. Nadel M, Srenson TI, Jerichau I, et al: Hepatobiliary 8. Klingensmith M, Johnson MC, Kuni CC, et al: Com scintigraphy with 99mTc-labelled diethyl acetanilide plementary role of Tc-99m diethyl IDA and US in iminodiacetic acid in the differential diagnosis ofjaun large and small duct biliary tract obstruction. Radio!- dice.Dan Med Buil27:278—280,1980 ogy 138:177—184,1981 21. Majd M, Reba RC, Altman RP: Hepatobiliary scintig 9. Kuni CC, Klingensmith WC, Fritzberg AR: Evalua raphy with 99mTc-PIPIDA in the evaluation of neo tion of intrahepatic cholestasis with radionuclide hep nataljaundice.Pediatrics67:140—145,1981 atobiliary imaging. Gastrointest Radio! 9:163—166, 22. Kuni CC, Klingensmith WC: Atlas of Radionuclide 1984 Hepatobi!iary Imaging, Boston, GK Hall Medical 10. Tidmore H, Ram MD: Hepato-biliary scintiscanning Publishers, 1983 in the evaluation of biliary enteric anastomoses. Am 23. Nicholson RW, Herman KL, Shields RA, et al: The Surg5l:158—l61,1985 plasma protein binding of HIDA. Eur J Nuc! Med 11. Williams W, Krishnamurthy GT, Brar HS, et al: Scm 5:311—312,1980 tigraphic variations of normal biliary physiology. J 24. Wiston BW, Subramanian G, Van Heertuan RL, et NuclMed25:160—165,1984 al: An evaluation of Tc-99m labelled hepatobiliary 12. Krishnamurthy GT, Lieberman OJ, Brar HD: Detec agents.JNuclMed 18:455—561,1977 tion, localization and quantitation of degree of com 25. Subramanian G, McAfee JG, Henderson RW, et al: mon bile duct obstruction by scintigraphy.JNuc!Med The influence of structural changes on biodistribution 26:726—735,1985 of Tc-99m labelled N-substituted IDA derivatives. J 13. Blue PW: Biliary scanning interpretation using Tc Nuc!Med 18:624,1977

1412 Lee,Ram,Shihet al TheJournalof NuclearMedicine