The daily secretion of one—twoliters of bile by theliver is continuous, but its entry into the intestine is eithercontinuous or periodic depending upon the time of need(1). After its secretion, the hepatic bile drains in twodirections; one fraction enters the small intestine directlythrough the common bile duct (continuous flow) and theother fraction drains into the gallbladder through thecystic duct. The entry of hepatic bile into the gallbladderis controlled primarily by the sphincter of Oddi, whoseincreased tone raises the pressure in the common bileduct, diverting the hepatic bile into the relaxed gallbladder during fast. When the gallbladder contracts,either because of ingestion of meal or upon injection ofcholecystokinin, it empties its contents first into thecommon bile duct and then into the intestine (periodicflow). The entire mechanism is under both nervous andhormonal control and normally is carried out in a wellcoordinated fashion. None of the current diagnostic tests

ReceivedJuly 14,1982;revisionacceptedNov. 8, 1982.For reprints contact G. T. Krishnamurthy, VA Medical Center

(I 15P),3710SW US VeteransHospital Rd., Portland,OR 97201.

allow the measurement of these biliary motor functionsnoninvasively and quantitatively (2). Some of the important questions that require answers are: 1. How muchof hepatic bile flows into gallbladder and intestine afteran overnight fast? 2. How soon and how long does thegallbladder contract following a single injection ofcholecystokinin? 3. How much does it empty? 4. Howmuch delay is there between gallbladder emptying andcommon bile duct emptying? 5. Is there bile reflux intocommon hepatic duct from the common bile duct duringgallbladder emptying? 6. What type ofchanges in biliarydynamics occur in patients with gallstones? To answerthese questions in patients, it is essential to establish thevalues in normal subjects. Ideally, a test should be simple,noninvasive, accurate, quantitative, short in duration,and widely available with minimum cost. In this cornmunication we report the results of a scintigraphic testfor biliary dynamics that fulfills all of the above criteria.The reproducibility of gallbladder emptying resultsobtained with pinhole and parallel-hole collimators wasestablished in rabbits in a comparison study

Volume 24, Number 3 217

QuantitativeBiliaryDynamics:Introductionof a NewNoninvasiveScintigraphic

Technique

Gerbail 1. Krishnamurthy, Vishnu A. Bobba, DonaldMcConnell, Fred Turner, MohammadMeSgarZadeh,and ElizabethKingston

VeteransAdministration Medical Center, and OregonNeafth Sciences University, Portland, Oregon

We useda Tc-99m-Iabeled hepatoblliaryagent to measurethe paditlonof hepaticbilebetweengallbladderandIntestineinsixteennormalpatientsandninepatientswithcholellthiasis.Innormalsubjects,thefractionsofthehepatlcbilethatflow Into the gallbladder and the small intestine were widely variable, with meanvaluesof 69 ±7% (s.c.) and 31 ±7% respectIvely.Bile refluxintothe commonhepaticductwas rare, occurrIngduringthe first2/3 of the gallbladderejectionpenod and onlywhenthe ejectIonfractionwas greater than 59%. The gallbladder'smeanlatentperiod,ejectionperiod,ejectionfraction,andejectionratewere2 ±I mm, ii ±i mm, 59 ±4%, and 5.9%/mm respectively. In patients with cholellthiasis,thefractionofhepatlcbileflowingIntothegallbladderwasnormal,buttheejectionfractionwas significantlyreduced(p <0.005). For an equIvalentdoseofcholecystoklnin,the gallbladderin cholelfthiaslsIs lessresponsivethan In normalsubjects.

J Nucl Med 24: 217—223,1983

KRISHNAMURTHY, BOBBA,MCCONNELL,TURNER, MESGARZADEH,AND KINGSTON

105

95@9o

@ 85@ 80

C

:@@

@ 700.‘n65

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FIG. 1. First-phasestudy.Hepatobiliaryimageat 10mm(A)showsgoodliveruptakeandslightkidney(K)excretionof Tc-99mHIDA.Commonbileduct,gallbladder,andintestineareseen,withkidneysinvisible beyond 30 mm (B). By 60 mm (C) most of radioactivityentersgallbladderandintestine.Regionsof interestaremated overentire gallbladder, intestine, and liver (background)as shown (D),andtime-activitycurvesaregeneratedfor entire60 mm(E).Sumof totalcountsIn60thframeovergallbladderandintestineareusedto calculate differential hepatic bile flow.

MATERIAL AND METHODS

Control subjects. Sixteen normal volunteers (10 maleand 6 female) ranging in age from 27 to 55 yr (mean age40), were chosen as controls. Women were not on oralcontraceptives. Gray-scale ultrasound studies showednormal bile ducts, with no stones in the gallbladder(3,4).

Patients. Nine patients with gallstones (7 men and 2women), ranging in age from 38 to 88 (mean 65) werestudied. The presence of stones in the gallbladder wasdocumented in all nine by ultrasound, and additionalconfirmation was obtained in four by oral cholecystography and also at surgery.

Data collection. This was carried out in two phases.

FIG. 2. Second-phasestudy. Selection of four regions of Interest:oneoverentiregamladder(GB)oneoverproximalcommonhepaticduct(CHD),includingdistalrightandleft hepatiCducts(RH& UI);oneovercommonbileduct(CBD);andoneoverliverto provideabackground(Bkg).

The first, lasting 60 mm, permitted the measurement ofrelative hepatic bile flow, and the second phase, lasting30 mm, monitored the biliary dynamics.

First phase. After an overnight fast, each subject wasgiven 5 mCi of Tc-99m HIDA (5) intravenously whilelying supine under a large-field gamma camera fittedwith low-energy, all-purpose, parallel-hole collimator.Serial, hepatobiliary analog images 2 mm each, wereobtained for 60 mm (Fig. 1). The information was simultaneously recorded in word mode on 64 X 64 computer matrices at 1 frame per mm, and stored on magnetic disk for later analysis.

Secondphase.Immediatelyafter completionof thefirst phaseof data collection, the gamma camera wasrefitted with a pinhole collimator (5 mm diameter) andfocused to include the gallbladder, common bile duct,and common hepatic duct as shown in Fig. 2. At 2-mmintervals the analog images were recorded for 30 mm andthe data were simultaneously collected in 64 X 64 matrixin the computer at 1 frame/mm. At 5 mm, 2 ml of salineplacebo was infused. At 10 mm, either 10 ng/kg (n = 15)or 40 ng/kg (n = 10)ofoctapeptide of cholecystokinin(OP-CCK) was infused intravenously over 3 mmthrough a Harvard infusion pump. The symptoms feltby the patient during the latent and ejection periods ofthe gallbladder were considered as biliary and symptomsat other times as non-biliary in origin.

First-phasedataanalysis.Onacompositeimagethatincluded 5 early and 5 late frames, three regions of interest (ROI) were chosen: one over the entire gailbiadder, a second over the abdomen (excluding the liver,gallbladder, and urinary bladder), and a third (background) over the liver, superior and lateral to the gallbladder (Fig. lA,B,C,D). The gallbladder and liver

48 52 56 60Time inMinutes after Injection of Tc99m-HIDA

218 THE JOURNAL OF NUCLEAR MEDICINE

CBD counts

CHD counts at peak time (Tn) —CHD baselinecounts

CLINICALSCIENCESDIAGNOSTICNUCLEAR MEDICINE

ROIs were of approximately equal size. The time-activity curves, for the entire 60 mm, were generated forthree regions and the counts were corrected for physicaldecay. The liver counts (background), from pixels equalin number to the total gallbladder pixels, were subtractedfrom the gallbladder to obtain the net gallbladder counts.The intestinal and gallbladder counts in the 60th frame(between 59 and 60 mm) were summed and consideredto represent total hepatic bile counts. The counts in thegallbladder and small intestine were used to calculatethe fractions of hepatic bile flowing into gallbladder andintestine (Fig. lE).

Second-phase data analysis. Four regions of intereston a composite Phase 2 image, consisting of five earlyand five late frames, were chosen (Fig. 2): the first overthe entire gallbladder (GB), the second over the commonhepatic duct (CHD) including the distal right and lefthepatic ducts (RH and LH), the third over the commonbile duct (CBD), and the fourth (background) over thesuperolateral aspect of the liver. The time-activity curveswere generated for each region, the background countswere subtracted, and the net counts decay-corrected andnormalized. The time from beginning of OP-CCKinfusion to the beginning of emptying (latent period),and the time from beginning to end of gallbladderemptying (ejection period), were noted (Fig. 3). Thegallbladder ejection fraction (EF) was calculated asdescribed earlier (6). The ejection rate was calculatedby dividing the percent ejection fraction by total ejectionperiod, expressed as percent ejection fraction per minute(Table 1).

From the CBD curve, (Fig. 3), the time from beginning of OP-CCK infusion to the peak (T1) and the timefrom the peak to new baseline (T2) were noted. In theabsence of a CBD peak, the time from OP-CCK infusionto the new baseline was considered entirely as the T2 time(Fig. 4).

Since the specific activity of hepatic bile after 60 mmis very low, usually no rise in CHD counts is noticedbeyond 60 mm. A rise in CHD curve counts (duringgallbladder emptying), ifany, over the baseline (beforeOP-CCK) wasconsideredas bilerefluxfromthe CBD.The reflux usually lasts during the gallbladder ejectionperiod and can be calculated for any period of time. Wehave chosen to calculate the reflux at its peak as shownon CHD curve. A reflux index for the common hepaticduct was calculated from the following formula:

I OK

0.5K

0

30K

25K

@ 20KC

@ 5K

aU, OK

3.OK@ Common Bile

@ Duct2OK@ /

‘0KL@ _____S 0 ‘5 20 25 30Timein Minutes

FIG. 3. Normal Biliary dynamics. Note no response to saline, andprompt emptying response to OP-CCKinfusion. Usuallyno refluxis seen into common hepatic duct. Gallbladderstarts to eject afterlatent period (I.?) of 2 mm. Ejection fraction (EF)of 58% is seendtringejectionperiod(EP)of 9 mm.Notepeakincurveforcommonbile ductduringlast 1/3of gallbladderejectionperiod.T1andT2timesare meassed as shown.

Comparisonof pinholewithparallel-holecollimator.Four New Zealand white male rabbits (3—5kg) with amean weight of 4 kg were studied twice within a periodof two weeks to test whether the pinhole and parallel-holecollimator studies would give comparable results. Exceptfor the change in collimators, the rest of the procedureremained identical in both studies, including the dose ofOP-CCK.

After an overnight fast, each rabbit was anesthesizedwith 50 mg/kg of ketamine and 5 mg/kg of Xylazineand was injected i.v. with 0.3 to 0.5 mCi of Tc-99mHIDA. Sixty minutes later, the animal was positionedsupine under the gamma camera. In the parallel-holestudy, the detector was positioned to include the entireabdomen; in the pinhole study it was placed to view thegallbladder, which was clearly visible in all rabbits by60 mm after injection ofTc-99m HIDA. The data wererecorded in a computer at 1 frame/30 sec for 30 mm in64 X 64 matrix. At 10 mm, 10 ng/kg ofoctapeptide ofcholecystokinin was infused over a 3-mm period througha Harvard infusion pump. The gallbladder ejectionfraction was calculated as described above for humans.The results were tested by paired Student's t-test for any

Peak hepatic =

duct reflux

index

— Baseline@ GB baseline GB counts

at time T@ CBD counts counts at time T@

The difference between the mean values was tested forany statistical significance by two-tailed unpaired Stu- statistical difference between the two means (Table 2).dent's t-test. p values of less than 0.05 were considered significant.

Volume 24, Number 3 219

220 THE JOURNAL OF NUCLEAR MEDICINE

KRISHNAMURTHY, BOBBA,MCCONNELL,TURNER, MESGARZADEH,AND KINGSTON

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CUNICAL SCIENCESDIAGNOSTICNUCLEAR MEDICINE

TABLE 2. COMPARISON OF PINHOLE WIThPARALLEL-HOLECOLLIMATORSFOR

MEASURINGGALLBLADDEREMPTYINGFOLLOWiNG A CONSTANT DOSE OF OP-CCK

IN RABBITS

4PTI5.0706025.0425233.0798743.08386Mean68.571.2

P > 0.05

tion fraction was 59 ±4%, with a mean ejection rate of5.9 ± 0.6%/mm. No reflux into the hepatic duct was

found during gallbladder emptying in 13 of 16 subjects,and in the remaining three subjects a reflux indexvarying from (41 to 45)% was found, either corresponding to or just before the onset of CBD curve peak.The CHD reflux did not last beyond the peak ofthe CBDcurve (Fig. 3). The CBD curve T1 and T2 times were 7±1 mm and 9 ±1 mm respectively.No untowardsymptoms were experienced by the subjects followingOP-CCK infusion.

Eleven normal subjects, in the initial stages, weregiven 40 ng/kg of OP-CCK; this was reduced to 10ng/kg in the last five subjects. The mean (±s.d.)ejectionfraction of (59.3 ±17)% obtained with 40 ng/kg, wasnot significantly different from that of (59.4 ±15)%obtained with 10 ng/kg dose (P<0.05). There were nodifferences in any of the other parameters between 10-and 40-ng/kg dose. Therefore, the two subgroups arecombined into one normal control group of sixteen.

Cholelithiasis. The mean fractional hepatic bile flowinto the gallbladder in patients with cholelithiasis was60 ±12% and was not different from that for normalsubjects (P>0.05). Following 10 ng/kg of OP-CCK, themean gallbladder latent period was 3 ±1 mm and theejection period 9.8 ±0.7 mm; these were similar to thevalues found in normal subject (P>0.05). The meangallbladder ejection fraction (38 ±6)% was significantlylower than that of the normal subjects (P<0.005), butthe ejection rate (4.1 ± 0.7)%/min was normal(P>0.05).TheshapeofCBDcurvewaslikethenormal(Fig. 3) in five patients, and the peak was absent in theremaining four (Fig. 4). No symptoms were felt by patients following OP-CCK infusion.

In four rabbits the mean ejection fractions were 68.5%and 71.2% by pinhole and parallel collimators respectively (Table 2), these not being significantly differentfrom each other (P>0.05).

Choielithiasis

a-

U,C

(3a,0

4

to i5 20 25Time in Minutes

FIG. 4. Billary dynamics In cholelithiasis. Uftrasound study (top),shows large gallstone with prominent acoustic shadow. BiliaryTc-99m HI@Aimages(middle)showuniformcaliberof commonbileduct,twistedneck,anda fillingdefect(S)dnetostone(left)atfundusof gallbladder,defect becominglessclear after OP-CCK(rI@it).Bilereflux into common hepatic duct is seen throughout gallbladderejection period, and curve for common bile duct shows no peak.Gallbladderejection fraction is 28% and ejection rate 3.1%/min.Note rapid gallbladderrefilling to % of its originalvolume,probablywith bile that had refluxed Into common hepatic duct (bottom).

RESULTS

Normal subjects (n = 16).The fractional mean (±s.e.)hepatic bile flow into the gallbladder was 69 ±7%, anddirectly into the small intestine 31 ±7%(Fig. 1E andTable 1). Following OP-CCK infusion, the mean latentperiod and the ejection period of the gallbladder were 2±0.3 mm and 11 ±1 mm respectively. The mean ejec

Volume 24, Number 3 221

KRISHNAMURTHY, BOBBA,MCCONNELL,TURNER, MESGARZADEH,AND KINGSTON

separable by any angulation tricks with the parallelcollimator, whereas they are easily separable by thepinhole.

Normal dynamics of the common bile duct. When thegallbladder ejects its bile into the common bile duct, theCBD curveshowsa rapidpeakoccurringin the last thirdofthe gallbladder ejection period (Fig. 3). We measurea time, T1, from the beginning ofOP-CCK infusion tothe CBD peak, but we are still not sure what T1 and T2(the falloff time) really measure.

Normal dynamics of the common hepatic duct. In threeof 16 normal controls there was 41% to 45% bile refluxinto common hepatic duct during gallbladder ejection.The peak reflux lasted only during the first and middlethird of the gallbladder ejection period. The ejectionfraction in these three was >58%, suggesting that thereflux index results from a recalcitrant sphincter of Oddi.No normal controls with ejection fractions <50% showedhepatic duct reflux.

Dynamics in cholelithiasis (n 9). One of nine patientswith cholelithiasis had a CHD reflux of4l%, with ejection fraction only 28%; the reflux continued through thelast third ofGB ejection (Fig. 4).

The cholelithiasis patients in general showed significantly lower GB ejection fractions than the controls(P<0.005), and only two exceeded 50%. Their gallbladders were evidently less responsive to intravenouscholecystokinin. The mean ejection rate of 4. 1 ±0.7 didnot differ significantly from that in the normal controls(P>0.05). Four of nine patients showed no rise in CBDcounts during gallbladder ejection (Fig. 4), and hadmuch lower ejection fractions (Table 1).

OP-CCK stimulation. The serum half-life of cholecystokinin is only 2.5 mm (26), so it is critical to maintainthe uniform dose rate of OP-CCK throughout the 3-mminfusion period. We found it rather difficult to achieveuniform dose rate by hand injection, and prefer theinfusion pump for a predetermined dose rate.

The 30-mm data collection is adequate (20 mm afterOP-CCK) for the dynamic phase of the study if OPCCK is used as the stimulus. The 13-mm sum of latentperiod (2 mm) and ejection period ( 11 mm) still leavesanother 7 mm for delayed gallbladder contraction indisease. With the short serum half-life of OP-CCK, thereis little chance of further ejection after the 20 mm.

Our recommended dose of OP-CCK (10 ng/kg over3 mm) is based on another study involving a largenumber ofsubjects (27,28), but somenormal gallbladders may not discharge even with a larger dose, so eachlaboratory should establish its own standard techniqueand dose rate for OP-CCK.

Potential application of current method. The currenttechnique is unique in several ways: (a) it is nongeometric; (b) does not require the use of contrast agents,catheters, or drugs in pharmacologic dose; (c) providessimultaneous anatomic and physiologic information; (d)

DISCUSSION

Hepatic bile flow. Tc-99m HIDA serves as the mostreliable bile marker for the evaluation of biliary physiology under basal conditions (7—JO).The large-fieldgamma camera (40 cm diam) permits the inclusion ofall of the areas between the left ventricle and the lowerabdomen to the levelof the urinary bladder (Fig. 1). Therelationship between counts and voluMe is close to linearunder parallel-hole collimator geometry (1 1). Thefractions of hepatic bile that partition between thegallbladder and intestine in normal people are widelyvariable. Our findings agree with those of others (12,13)in showing that—granted a patent cystic duct—thefraction of hepatic bile flowing into the gallbladder incholelithiasis is entirely within normal limits.

Pressure differences are known to exist at variouslevels of the biliary tree. In humans the resting mean(and range) pressures in the sphincter of Oddi commonbile duct, and in the gallbladder are 15 (9—23),12(10—15),and 10 (8—12)cm of water respectively (14—17). Pressures as high as 100 mm of mercury have beenrecorded across the sphincter of Oddi (18—23).Thesphincter normally shows alternate contraction and relaxation at a frequency of 7.5 per mm. The pressure fallsto the CBD level during relaxation, allowing the bile topass from CBD to duodenum, whose pressure normallyis zero (22).

Normal gallbladder dynamics. Since the typicalpressure rise between the gallbladder and the commonbile duct is normally less than 2 cm of water, the gallbladder can contract and overcome the CBD pressureeasily, starting ejection as early as 2 mm, usually duringOP-CCK infusion. The gallbladder discharge lasts I 1mm, with a mean ejection fraction of 59% (range 35 to89%);themeanejectionrate isthusc@6%/min.In onlytwo control subjects was the ejection rate less than3.5%/mm (Table 1).

The sphincter of Oddi can withstand a mean pressureof I5 cm of water (range 9—23cm) in CBD (24). Thismeans that the contracting gallbladder should generatepressures exceeding 15 cm of water to empty its contents.The results of our study show that the gallbladder accomplishes this in about I I mm following OP-CCKinfusion.

The method described here does not require any assumption of a particular shape for the gallbladder, andthus it overcomes the major limitation of those tests thatare geometry dependent. Ultrasound, for example, incursa mean error of I7% for gallbladder volumes less than@-‘l7cc (25).

Pinhole collimators limit the field of view to the primary region of interest and provide the clear separationof gallbladder, common bile duct, common hepatic duct,and upper small intestine. On some occasions, thegamma images of these structures at 60 mm are not

222 THE JOURNAL OF NUCLEAR MEDICINE

CLINICAL S(@WNCFS

DIAGNOSTICNUCLEAR MEDICINE

allows precise identification of time of filling, emptying,and refilling of the gallbladder (Fig. 4C); and (e) theresults are quantitative. All the components required forthe study (gamma camera, computer, and radiopharmaceuticals) are already available in most nuclearmedicine departments, and the radiation dose is withinsafe limits (29). The entire data collection takes about90 mm, and this can be reduced to 30 mm if only dynamic data are of interest. The prime areas where thistechnique is applicable are: (a) in the study of the effectof drugs on biliary function; (b) to furnish indicationsfor, or monitor the effects of, endoscopic or surgicalsphincterotomy; (c) in biliary dyskinesia; (d) for thequantitation of partial CBD obstruction based on gallbladder ejection rate; and (e) in the study of nervous andhormonal effects on biliary dynamics. We hope that thisapproach will enable the physician to unravel the unknown of biliary pathophysiology noninvasively.

ACKNOWLEDGMENT

This project supportedby VeteransAdministration.

REFERENCES

I. WHEELER HD: Secretion of bile. In Diseasesofihe Liver,Philadelphia, JB Lippincott Co, 1975,pp 87—110

2. SHERLOCKS: Diseasesof the liver and biliary system.London, Blackwell Scientific Publications, I975

3. GROSSMANM: Cholelithiasisandacousticshadowing.J ClinUltrasound6:182-184,1978

4. FERRUCCIJT: Body ultrasonography, Part II. N EnglJ Med300:590-602, 1979

5. LOBERGMD, COOPERM, HARVEY E, et al: Developmentof new radiopharmaceuticals basedon N-substitution of iminodiacetic acid. J Nuci Med I 7:633-638, 1976

6. KRISHNAMURTHY GT, BOBBA VR, KINGSTON E: Radionuclide ejection fraction: A technique for quantitativeanalysis of motor function of the human gallbladder. Gastroenterology 80:482-490, 1981

7. LOBERGMD, FIELDSAT: Chemicalstructureof Tc-99mlabeled N-(2.6-dimethylphenylcarbamoylmethyl)-Iminodiacetic acid (Tc-99m HIDA). mt J Appi Radiat Isot 29:167-173,1978

8. HARVEY E, LOBERGMD, RYAN J,etal: HepaticclearancemechanismofTc-99m-I-IIDA and its effect on quantitationof hepatobiliary function: Concise communication. J NuclMed 20:310-313,1979

9. RYAN J, COOPERM, LOBERGMD, et al: Tc-99m labeledN-2.6,-Dimethylphenylcarbamoylmethyl) iminodiacetic acid(Tc-99m HIDA), a new radiopharmaceutical for hepatobiliary imaging studies.J Nuci Med I 8:997—1004, 1977

10. BROWN PH, KRISHNMURTHY GT, BOBBAVR, Ctal: Radiation dose calculation for Tc-99m HIDA in health anddisease.J Nucl Med 22:177- I 83, 1981

II. CHAUDHURITK: Useof@―Tc-DTPAfor measuringgastricemptying time. J Nuci Med I 5:391-395, 1974

/2. SHAFFEREA,MCORMONDP,DUGGANH:Quantitativecholescintigraphy: Assessment of gallbladder filling andemptying and duodenogastric reflux. Gastroenterology 79:899-906, 1980

13. HENEGOUWEN GPV, HOFMANN AF: Nocturnal gallbladderstorageandemptying in gallstonepatientsand healthsubjects.Gastroenterology 75:879—885,1978

14. MIRANDA M, ESPINOZAM, CENDESA: Manometriccharacterizationof the extrahepaticbiliary tracts in dogs.DigDisScience 26:417—422,1981

15. POOULI J, GEENEN JE, HOGAN WJ: Sphincter of Oddimotor activity: A comparisonbetweenpatients with commonbile duct stoneand controls. Gastroenterology 82:111-1 14,I982

16. ANDERSONMC, HAGSTROMWJ: A comparisonof pancreatic and biliary pressurerecordedsimultaneously in man.CanfSurg 5:461-470, 1962

17. BERGHGS, LANE JA: A demonstration ofthe independentcontractionof thesphincterof thecommonbile duct in humansubjects.Am I Physiol I 28:690-694, 1940

18. SMITH JL, WALTERSJL, BEAL JM: A study of choledocalsphincter action. Gastroenterology 20:129-137, 1952

19. CUSHIERIA, HUGHESJH, COHENM: Biliary pressurestudies during cholecystectomy. Br J Surg 59:267-273,I972

20. BERGHGS: The sphinctermechanismof the commonbileduct in human subjects: Its reactions to certain types ofstimulation. Surgery 11:299-330, 1942

21. CRISPIN JS, CHOI YW, WISEMAN DGH, et al: A directmanometricstudy in the caninecholedochoduodenaljunction.ArchSurg 101:215—218,1970

22. CSENDESA, KRUSEA, FUNCH-JENSENP,et al: Pressuremeasurementsin the biliary and pancreatic duct system incontrols and in patients with gallstones previous cholecystectomy, or common bile duct stones.Gastroenterology 77:1203-1210,1979

23. GEENEN JE, HOGAN Wi, DODDSWJ, et al: Intraluminalrecording from the human sphincter of Oddi. Gastroenterology78:317-324,1980

24. SCHOFIELDLi: Physiologyofihebiliarysystemindiseaseofthe gallbladderandbiliary system.NewYork,JohnWiley& Sons, 1977

25. EVERSONGT, BRAVERMANDZ, JOHNSONML, et al: Acritical evaluation of real time ultrasonography for the studyof gallbladder volume and contraction. Gastroenterology79:40-46, 1980

26. THOMPSON JC, FENDER HR. RAMUS IN, et al: Cholecystokinin metabolism in man and dogs. Ann Surg I 82:496-504,1975

27. KRISHNAMURTHYGT, BOBBAVR, KINGSTONE: Optimum OP-CCK dose for gallbladder (GB) emptying. C/inNuclMed9:451, 1981(abst)

28. KRISHNAMURTHYGT,BOBBAVR,KINGSTONE:Optimization ofcholecystokinin (OP-CCK) dosefor gallbladderemptying. In The Proceedingsofthe Third World Congressof Nuclear Medicine and Biology. Raynaud C. Ed. Paris,France, Pergamma Press,Vol 2, 1982, pp 2244-2247

29. BROWNPH,KRISHNAMURTHYGT, BOBBAVR: Radiationdosecalculation for five Tc-99m-IDA hepatobiliary agents.I Nuci Med 23:1025-1030, 1982

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