Dean

D. T. Maglinte,

MD

#{149} William

E. Torres,

Oral Cholecystography Gallstone Imaging: The introduction of nonoperative alternatives to elective cholecystectomy in the management of gallstones has resurrected use of oral cholecystography (OCG). This article reviews basic principles involved in the proper performance of OCG and interpretation of the resulting images. The role of OCG in the current management of gallstones is discussed. Index

terms:

Gallbladder,

Gallbladder, der,

US

studies,

Radiology

1991;

From

the

Center

diology, Hospital

Department of Indiana, IN

Lithotripsy versity and and gy,

the

for

of Radiology, 1701 N Senate

46206

(D.D.T.M.);

the

Crawford

Long

Department School

and

of

Radiology,

of Medicine,

the Sections of Biliary Lithotripsy,

Ra-

Methodist Blvd. IndiBitiary Hospital Emory

Atlanta

Gastrointestinal Department

Radiology of Radiolo-

of the

University

of Pennsylvania,

(IL.).

Received

14, 1990; received

10; accepted

requests to D.D.T.M. c RSNA, 1991

August

June 18; revision 22.

Uni-

(WET.);

Hospital

July

Liver

of Gastrointestinal

Philadelphia vision requested gust

#{149}

#{149} Gallblad-

Gallbladder

Section

Center,

the

762.289

178:49-58

and

anapotis,

762.1221

762.1298

Diseases

and

calculi,

radiography,

Address

reprint

reAu-

MD

#{149} Igor

Laufer,

MD

in Contemporary A Review’ The

reports

exaggerated.

S

of my

death

[Mark

are

Twain,

greatly

1897]

for evaluation of the gallbladder depend primarily on two factors: the physician’s therapeutic goals and the patient’s clinical presentation (1). In the management of gallstone disease as alternatives to traditional elective cholecystectomy increase in popularity, the accurate imaging of gallstones has become more demanding. The introduction of orally administered bile acid therapy, contact dissolution (lavage chemolysis), and extracorporeal shock wave lithotripsy (ESWL) require information regarding size, number, composition of stones, and determination of patency of the cystic duct. These needs have resurrected oral cholecystography (OCG). The proper performance of 0CC and interpretation of the images require an understanding of the pharmacology of biliary contrast materiais, appropriate patient preparation, and the avoidance of technical pitfalls (2). The issue in the late 1970s and early 1980s was whether to perform 0CC at all in light of advances in ultrasonography (US) and radionuclide scintigraphy (3). In 1990 we need to refocus on an old tool to anTRATEGIES

swer specific new questions. This article reviews basic principies of patient preparation, contrast material excretion pathways, principies of interpretation, and technical considerations in the performance of 0CC. The way in which the test is performed should be tailored to answer the above questions most efficiently. The role of 0CC in the current management of gallstones is discussed.

HISTORICAL The sidered stones

gy (4). The technique is based on the principle of selective excretion of a radiopaque contrast medium predominantly by one organ system with evaluation of that system by radiologic methods. It is the result of the research efforts of two distinguished surgeons, Drs Evarts Graham and Warren Cole (hence the earlier eponym Graham-Cole study). The first successful cholecystogram was obtained from a dog in November 1923 (5). The first successful demonstration of the gallbladder in a patient was reported in 1924 (6). It was achieved with an intravenous infusion of calcium tetrabromophenolphthalein. The first successful visualization of the gallbladder with an orally administered contrast agent was reported in 1925 with use of sodium tetraiodophenolphthalein (7). The development of biliary contrast agents laid the groundwork for the general development of radiopaque contrast media.

BILE

AND

THE

ENTEROHEPATIC CIRCULATION An understanding of the function of bile and the enterohepatic circulation is necessary for proper patient preparation. Bile is necessary for solubilization and absorption of intestinal fat. It is the main pathway for the excretion and metabolism of cholesterol and diverts many toxins, including bilirubin, away from the bloodstream. Each day, 250-1,100 mL of bile is manufactured in the liver and flows through the intrahepatic ductal system into the common bile duct. Flow is retarded at this level by contraction of the sphincter of Oddi,

PERSPECTIVE

development of 0CC is conone of the important milein the history of roentgenolo-

Abbreviations: wave der; methyl

ESWL

lithotripsy; OCG

=

oral

tert-butyt

KUB

extracorporeal

kidney,

cholecystography;

shock

ureter, MTBE

blad=

ether.

49

which forces bile through the cystic duct and into the gallbladder. Bile is concentrated in the gallbladder, primanly as a result of the active transport of sodium, chloride, and bicarbonate across the gallbladder epithehum. After the ingestion of a fatty meal, cholecystokinin is released from the duodenal mucosa. This stimulates gallbladder contraction and simultaneous relaxation of the sphincter of Oddi, thereby emptying bile salts into the duodenum. Bile salts are steroid compounds that are synthesized from cholesterol in the liver, excreted into the bile, and stored in the gallbladder in the fasting state. When these salts reach the terminal iheum, they are actively reabsorbed from the intestine, nearly completely taken up by venous blood then reexcreted

the

liver in one into

CONTRAST

from the circulation, the bile.

portal and

AGENTS

Tetrabromophenolphthalein was the initial contrast agent developed 60 years ago (5). In ensuing years, other contrast agents that were more rapidly absorbed and excreted and that produced less unpleasant side effects were developed (Table 1). Much of our current understanding of contrast materials for 0CC is the result of the research efforts of Berk and colleagues (8,9). lopanoic acid, the most popular 0CC agent in the United States, was developed in 1951 to improve opacification and diminish gastrointestinal side effects (10). It is a triiodobenzene ring compound and is the most lipid-soluble 0CC agent. Subsequent compounds that have been developed, such as ipodate calcium and ipodate sodium, tyropanoate sodium, and iocetamic acid, differed from iopanoic acid in the one and three positions in the ring. The hatter agents have varying degrees of aqueous and lipid solubihity.

ABSORPTION EXCRETORY

AND PATHWAYS

0CC contrast agents are absorbed by means of passive diffusion across the mucosa (11-14). For this to happen, the contrast agents must first dissolve in the aqueous environment in the intestinal lumen. The cornpound must then diffuse through the lipid cell membrane of the intestinal mucosa. Absorption, therefore, requires dissolution of the compound first in water and then in lipid. Since iopanoic acid is lipid soluble and 50

.

Radiology

Table OCG

1 Contrast

Agents

and

Iodine

Content % Organic

Contrast lopanoic

acid

Agent

Bound

Preparation*

Iodine 66.7

0.5

Ipodate calcium (Oragrafin calcium)l Ipodate sodium (Oragrafin sodium)l Tyropanoate sodium (Bibopaque)t

61.7 61.4 57.4

3.0 0.5 0.75

Iocetamic

62.0

0.75

acid

(Tetepaque)t

(g)

(Cholebrine)l

* The recommended dose of each compound t Winthrop-Breon Laboratories, New York. I Squibb, New Brunswick, NJ. I Mallinckrodt, St Louis.

is 3.0 g.

only partly water soluble, bile salts are essential for its absorption (15). The addition of fat to the diet irnproves its absorption by stimulating the enterohepatic recirculation of bile salts. Since the intestinal blood barrier is lipoidal, iopanoic acid is readily absorbed into the bloodstream. Once in the bloodstream, iopanoic acid binds to albumin and is transported to the liver. In the liver, the cholecystographic agent is conjugated with glucuronic acid by the hepatic microsornes and is rendered water soluble (16). After conjugation, iopanoic acid is excreted into the bile canaliculi, and ultimately the majority of it enters the gallbladder through a patent cystic duct. A portion of the bile is lost by direct flow into the duodenum. Compounds that are highly soluble in water but insoluble in fat are easily solubihized in the water in the intestinal lumen but cannot move across the lipid boundary of the intestinal mucosa. The excretion of the newer cholecystographic agents by the liver is not affected by bile salts or the absence of fat from the diet.

CONCENTRATION CONTRAST

MATERIAL GALLBLADDER

OF IN THE

Reabsorption of water by the gallbladder mucosa leads to iopanoic acid concentration and gallbladder opacification. A concentration of 0.25%-1.0% iodine is required in the gallbladder for radiographic visualization (17,18). Peak opacification occurs on the average of 17 hours after ingestion of iopanoic acid (range, 1419 hours) (19). The other cholecystographic agents result in more rapid opacification. Ipodate calcium granules may produce opacification as soon as 5 hours after ingestion; these granules are most often used in conjunction with a single overnight 3-g

dose of a cholecystographic agent and is especially helpful in those patients awaiting discharge from the hospital (5-hour reinforcement cholecystography) (20). Peak radiographic visualization with tyropanoate sodium occurs at 10 hours (21,22). The failure to visualize the gallbladder in the absence of cystic duct obstruction or extrabiliary causes reflects failure of the gallbladder to reabsorb water and concentrate the contrast material (5). The possibility that reabsorption of the contrast material from the gallbladder could resuit in nonvisualization was recognized in the past (23). In modern times, Berk and Lasser conclusively showed that conjugated iopanoic acid is readily absorbed from the inflamed gallbladder (24). They emphasized the importance of this mechanism as a cause of nonvisualization. Gallbladder opacification may also be impaired in fasting patients including patients with acute pancreatitis who are fasting as part of their therapy because of the absence of circulating bile salts. Impaired visualization of the gallbladder in patients who are receiving a low-fat diet and are given iopanoic acid is the result of poor absorption and excretion of contrast agent rather than stasis of nonopaque bile in the gallbladder (2,25). It is, therefore, important for patients scheduled to undergo 0CC with iopanoic acid to ingest a meal containing fat prior to oral intake of the contrast agent to ensure efficient absorption of the agent. In patients who cannot ingest fat, the examination should be performed with agents such as tyropanoate sodium or ipodate instead.

DOSAGE

AND

SIDE

EFFECTS

The dosage schedule advocated by Burhenne and Obata (26) is the most practical regimen for outpatient imaging. Use of the 2-day consecutiveJanuary

1991

2a.

Figures

1, 2.

onstration

of

(1) Overpenetrated

OCG

image

2b.

showing

calcium-rimmed

radiolucent

stone

(arrow).

KUB 0CC

radiograph

is unnecessary

for

dem-

right, no stones are evident. Preliminary radiograph obtained 1 day later. Stained

image obtained with the patient upKUB radiograph was unremarkable. (b) Contrast material-stained small stones (arrow) in upright stones were suspected on KUB radiograph obtained prior to a barium enema examination, and the

upright

prior

spot

calcium

in

radiographs

this

situation.

were

(2)

obtained

Contrast

material

to

the

staining

procedure.

of

This

was

calculi.

(a)

On

confirmed

the

at

2nd-day

gallbladder

b. Figure shown ing

right

3. Absorbed versus nonabsorbed oral OCG agent. (a) Absorbed oral contrast in the right and left sides of the colon as faint homogeneous excreted material

lumen.

side

(b)

Unabsorbed

contrast

agent

is manifested

flaky

material

seen

in

the

of colon.

dose schedule eliminates 15%-50% of all repeat gallbladder examinations required (27-30) and avoids falsepositive diagnoses. With this dosage schedule, the patient needs to make only one trip to the radiology department. The failure of the gallbladder to opacify with use of this dosage schedule is highly suggestive of intrinsic gallbladder disease (obstruc-

Volume

as dense

agent outlin-

178

#{149} Number

1

of cystic duct or nonobstructive cholecystitis) when extrabiliary causes of nonvisuahization are excluded. In inpatients, an efficient method is a single dose of 3 g of iopanoic acid. If a second dose is necessary, 3 g of ipodate calcium granules is given and radiography is performed 5 hours hater. In the 2-day consecutive dosage tion

is

US examination.

schedule, the patient follows a lowfat diet for 2 days before the day of examination; on the 1st day, two tablets are taken after lunch, and two more tablets are taken after supper. On the 2nd day, two tablets are taken after breakfast, lunch, and supper; the last two tablets are taken at 8:00 PM (a total of 12 tablets, or 6 g of iopanoic acid, are given during the 2day period). Nothing is eaten after the evening meal on the 2nd day (juices and black coffee or tea with sugar are encouraged until bedtime). Laxatives are not given as the cholecystographic agents will inherently produce slight diarrhea. If excessive diarrhea occurs, the tablets are discontinued, and the patient reports for radiographic examination on the following morning. The patient should not eat solid foods on the morning of the 3rd day before reporting for the examination (however, juices and black coffee or tea with sugar are encouraged) (26). When the last tablets are taken no later than 8:00 PM, imaging is optimal at 10:00 AM the next morning. Good hydration is encouraged to reduce the risk of renal toxicity from the uricosuric effects of the contrast agent (31). There is evidence that massive doses of contrast material may involve a small risk of renal shutdown in patients with hepatorenal damage. The

Radiology

.

51

b.

a.

C.

Figure 4. Location of stone and patient position. (a) With the patient in the upright position, the stone (arrow) will gravitate to the most inferior portion of the gallbladder, the fundus. Note that a stone can be arrested from dropping into the fundus at the infundibulum or Hartmann pouch (H). Focal dilatation creates a dependent wall in this position. (b) With the patient in the supine position, the stone (arrow) tocalizes in the body and part of the Hartmann pouch. The infundibulum and the neck are common areas where small stones or fragments may hide. (c) With the patient in the prone position, the stone (arrow) localizes in the fundus, the widest and most anterior portion of the gallbladder

that

usually

protrudes

fragments are easily measured tance) compared with those

beyond

and for

other

the

counted

TECHNICAL CONSIDERATIONS Abdominal

It has been shown that a prelirni14 X 17-inch kidney, ureter, bladder (KUB) radiograph taken on the day prior to the examination obviates cholecystography in only 9% of patients who have unequivocal opaque calculi; in less than 2% of patients, calculi will be obscured by contrast material (33). This routine was, therefore, discontinued. The use of a preliminary radiograph, however, has been recently resurrected because of the need to determine the presence of gallstone calcification for many of the nonsurgical alternatives to elective cholecystectomy. Visible calcification is believed to be due to calcium carbonate and calcium phosphate. The calcium concentration is sufficient to be visible on plain radiographs in only 10%-15% of patients (34). A radiograph obtained with the patient in the prone position is preferred to one obtained with the patient supine, as the abdomen is corn-

nary

52

.

Radiology

of

position

the

liver

because

and

comes of

sharper

in

contact radiographs

with

the and

anterior lesser

abdominal magnification

wall.

Small

(shorter

stones target-film

or dis-

views.

gallbladder may also become extremely dense, making it more difficult to identify small stones. Side effects such as mild diarrhea (which occurs in 23% of patients), dysuria (in 14%), mild nausea (in 6%), and vomiting (in 0.5%) are aggravated by unnecessarily large doses (32). Severe diarrhea occurs in a few patients (2.5%).

Preliminary Radiography

margin

in this

pressed motility

against the table and bowel is reduced. If the preliminary KUB radiograph cannot be obtamed prior to 0CC, the radiograph may be obtained at a later date if the 0CC images do not suggest calcification (Fig 1). Calcifications can be mimicked by iopanoic acid, which can cause “staining” of radiolucent gallstones after repeated doses (Fig 2) (35). The KUB radiograph obtained after contrast material administration, therefore, does not ideally substitute for one obtained before contrast material administration because of the phenomenon of staining and the presence of milk of calcium bile, which can simulate a contrast material-filled gallbladder. Both conditions are, however, rare. If the gallbladder is not immediately seen at fluoroscopy in its usual position, a KUB radiograph is obtamed. This is done to localize the gallbladder and determine whether opacification is adequate to complete the fluoroscopic portion of the examination. The gallbladder may not be in the usual location. It can overlie the spine or may be in the pelvis or left hemiabdomen. By imaging the entire abdomen, abnormalities preventing absorption of iopanoic acid, such as gastroduodenal ulcers, malignancy, or retention of contrast material in a large esophageal or duodenal diverticulum, can be seen (3644). Dense, flaky, unabsorbed contrast material should be distinguished from the uniform faint

Spot Radiography Gallbladder

opacification of excreted conjugated contrast material (Fig 3) (45).

The anatomic configuration of the gallbladder and the positioning of the patient determine where stones localize in the gallbladder. Acquisition of radiographs with the patient in the upright, supine, and prone positions with various oblique views to remove superimposed gas should be routine (Fig 4). The upright radiograph is necessary to demonstrate buoyancy. Decubitus radiographs achieve the same purpose as upright radiographs; however, they are technically more difficult to obtain. Good grid alignment and the placement of the gallbladder in the center of the beam may be difficult to achieve with the patient in the lateral decubitus position. The gallbladder may be obscured by superimposed ribs in this position. Radiographs obtained with the patient in both supine and prone positions allow separation of multiple stones for confident determination of size and number. The supine radiograph is necessary to fully visualize the infundibulurn and neck, areas where small stones or fragments may hide and occasionally may not be appreciated at 0CC or US (Fig 5). Generally, a low-kilovoltage technique (60-70 kV) is used for contrast material enhancement; however, a higher kilovoltage setting should be used if there is dense concentration of contrast medium. The kibovoltage peak setting should be adequate, as underpenetration can result in a

of the

January

1991

demonstration of a normal common bile duct obviates a more invasive or expensive diagnostic workup. Occasionally, a gallbladder obscured by bowel gas may be visualized to better advantage after a fatty meal. The assessment of gallbladder contraction to help predict which patients are able to eliminate gallstone fragments appears unreliable. The lack of gallbladder contraction following a fatty meal or intravenously administered cholecystokinin is of unproved clinical significance.

Plain Upper

b. Figure 5. Stone arrest in nondependent segment. (a) Upright radiograph shows no evidence of stone in fundus. (b) Supine view demonstrating tamelbated calculus (arrow) at junction of neck and cystic duct (confirmed at surgery).

Tomography Quadrant

This

is an

employed

of the

excellent

Right

adjunct

in cases

when

of suboptimal

vi-

sualization or nonvisuahization of the gallbladder. Tomography can demonstrate opacification of the common bile duct in the absence of gahlbladder visualization in 70%-80% of pa-

tients

(50-52).

This

occasionally

al-

lows visualization of small stones obstructing the cystic duct that may be difficult to identify on plain radiographs or US scans. Tomography will also help identify stones that are not

obvious

on plain

radiographs.

PRINCIPLES INTERPRETATION

b. Figure 6. Radiographs ease. (a) OCG image echogenic though ter

terot

obtained

obtained

after

before

a fatty

ingestion

structure seen on US scans. overall opacity of gallbladder

ingestion

of

a fatty

meal

shows

meal

in

patients

with

benign

gallbladder

meat because of nonshadowing Cholesterol plaques are not shown convincingly, appears inhomogeneous. (b) OCG image obtained

scattered

dis-

of a fatty

cholesterol

polyps.

Arrow

points

to

one

atafcholes-

plaque.

false-negative study even with large stones. Compression can also be employed to penetrate the densely opacified gallbladder. The use of 12:1 grids and low kibovoltage-peak settings achieves maximum contrast and minimum scatter (46,47). Close colhimation is important.

Radiography

after

a Fatty

Meal

Although it has been shown in one study (48) that the best technique for detecting calculi is acquisition of decubitus radiographs 20 minutes after ingestion of a fatty meal, this practice was abandoned following the results of a study that showed that the yield is seldom worth the effort (49). Acquisition of radiographs after a fatty meal should be reserved for specific

Volume

178

#{149} Number

1

situations. They should be obtained if the initial radiographs do not show stones or if poorly defined defects are suspected. By stimulating gallbladder contraction, the RokitanskyAschoff sinuses, characteristic of adenomyomatosis or the plaques of cholesterolosis, may be seen (Fig 6). Radiographs obtained after a fatty meal will also help diminish the frequency with which small stones or fragments are obscured by the density of the contrast material and will show the neck and cystic duct segments to advantage. In many instances the common duct may also be shown. Demonstration of a normal common duct is important if the patient is ineligible for the nonsurgical alternative protocols and laparoscopic cholecystectomy is planned. The

OF

There are tered in the 0CC findings

a few problems interpretation may include

one

gallstones

or more

quate

tion.

opacification

When

and

made-

or nonopacifica-

there

fication of the of possibilities nonvisualization)

encounof OCCs. either

is poor

gallbladder, (extrinsic must

or no opacia variety causes of be considered

including (36-44) (a) failure of the patient to take the contrast material (faulty instruction or poor compliance); (b) obstructive upper gastrointestinal diseases including retention in the esophagus (hiatal hernia or diverticulurn), stomach (ulcers or tumors), or duodenum (ulcer, diverticulum); (c) failure of intestinal absorption as in profound diarrhea, with a decrease in intestinal bile salts in fasting patients, with a loss of bile salts secondary to terminal ileum abnormality or rapid transit time (io-

panoic

acid

absorption);

overdose (d) liver

hepatocehlular ary canalicular

results

in non-

dysfunction

diseases and or extrahepatic

in

with

bilibihiary

obstruction; and (e) prior cholecystoenterostomy or cholecystectomy. The exclusion of the above factors

or the terial

nonabsorption in a nonvisualized

of contrast

ma-

gallbladder

Radiology

.

53

after the 2-day dosage schedule or 5hour reinforcement method indicates intrinsic gallbladder disease. Identification of residual absorbed contrast agent in the small intestine or colon indicates that contrast material was ingested, absorbed by the proximal

small and duct

bowel,

excreted

by the

passed through the and the duodenum

Nonvisualization with opacification

liver,

common (Fig 3a).

of the gallbladder of the common

duct at 0CC is evidence of cystic duct obstruction. The performance of tomography in these equivocal cases permits a positive diagnosis of cystic duct obstruction instead of an mdirect diagnosis of nonvisualized gallbladder consistent with gallbladder disease in the absence of extrabiliary causes for nonopacification. This equivocal reporting has been one of the objections to the use of 0CC in the past and should be avoided. The nonopacification of the gallbladder or the common bile duct following identification of absorbed and excreted contrast material in bowel suggests impaired water absorption by the gallbladder or contrast material

diffusion

through

the

inflamed

gall-

bladder wall (intrinsic gallbladder disease). The absence of opacification of both the gallbladder and the bile duct without the presence of opaque gallstones and without absorbed con-

trast

material

in the

small

bowel

or

colon suggests cation other The primary

on

US

studies

Errors

in the

interpretation

images are primarily only partly perceptive.

to technical terpretive

details

helps

of the technical Attention ensure in-

accuracy.

OCG VERSUS CHOLECYSTOSONOGRAPHY

less

than

5 years

after

the

introduc-

tion of sonography, 0CC all but disappeared from clinical practice (53,54). Real-time US is simple to perform, noninvasive, without ionizing

radiation,

and

independent

of hepat-

ic function; it offers several advantages over 0CC, and in the last decade has been shown to be a practical modality for the evaluation of both the gallbladder and the biliary sys54

#{149} Radiology

are

bladder

in

a fatty

one

of

visible

of the

the

the

diagnosi

meat

shows

stones

between

ed. With

and

gallstones (58).

suggested

galltwo

A report

that

causes exclud-

of 0CC

is closer in the

technically

con-

duct or to-

of US,

accuracy

of

to 85%early

1980s

good

0CC

is superior in sensitivity and specificity to real-time cholecystosonography in the diagnosis of gallbladder disease (59). However, the 0CC images must be of meticulous quality

must

be interpreted

properly,

otherwise the sensitivity and specificity would be comparable to or fall below that of US scans. In the diagnosis of gallbladder disease, 0CC is used predominantly to complement cholecystosonography in cases in which US findings have failed to demonstrate evidence of gallbladder disease in light of strong clinical symptoms or in which US findings have demonstrated nonspecific abnormahities (60). A recent report has

questioned cupy

modality

the

whether role

for

0CC

of primary

the

detection

small

stones

cursors).

bladder

disease

(61).

This

is because

of the lack of a significant difference in sensitivity between the two methods. In this report, however, benign gallbladder disease was included. A close evaluation of how often cholelithiasis was demonstrated at 0CC in this report showed that only 65% of patients with proved cholehithiasis

stones

that

were

demonstrated

at

and

is nonvisuahi-

availability

the

(b) Multiple

in de-

there

extrabiliary have been

contraction.

data

opacified on

the

had

when

in an

gallbladder

the

that

tecting

correct

minimal

0CC while 93% had stones that were demonstrated at US (60). 0CC is more sensitive than US in the diagnosis of benign gallbladder diseases (59,61). The demonstration of benign gallbladder disease in addition to stones has not entered into decisions regarding eligibility for alternative gallstone therapy. Sonography is widely accepted as 15%-20% more sensitive than 0CC

interpretation

studies (the common at plain radiography

mography) nonvisuahization

90%

the

is 100%

or when

secutive visualized

and

0CC was the unchallenged standard of reference in the diagnosis of gallbladder disease for 50 years, but

that

images

stones

show

0CC and

on

show

of 0CC

US and (3).

(arrow

images

after

volved only patients in whom positive 0CC findings were correlated with surgical findings (57). Such

zation

examinations

scan

US

tern and adjacent organs. With use of state-of-the-art techniques, diagnostic accuracy of 90%-95% in the detection of stones has been reported (55,56). Previous reports indicating an accuracy rate for 0CC as high as 99% are misleading in that the studies in-

causes for nonopacifithan gallbladder disease. diagnoses of gallstones or of cystic duct obstruction in emergent situations, however, are more efficiently achieved with gallbladder

radionuclide

,

a. Figure 7. OCG and OCG image obtained

should screening

of gall-

oc-

has

a lower

false-negative

rate

(62,63). The ability of US to help detect gallstones, especially those in the range of a few millimeters, has been amply demonstrated (Fig 7). However, the need to count and size gallstones and assess cystic duct patency has resurrected the use of 0CC. Recent clinical experience has shown that accurate measurement of large stones is difficult with US. Measurement of gallstone size on US scans is

accurate

with

stones

smaller

than

2

cm, but is less accurate with gallstones larger than 2 cm (Fig 8) (64). This difficulty is attributed to the acoustic reflection and absorption of the ultrasound beam obscuring the deep and polar surfaces of large gallstones. Restricted lateral resolution limits sonographic measurements of larger stones to the axial plane. Callstones on US scans are often contiguous or overlapped and are difficult to

size

and

number.

The

superiority January

of 1991

cols

(ie, in sizing

fragments).

In

many cases, gallstone fragments that result from hithotripsy clump together and are difficult to size accurately with US. In our experience, the concomitant use of 0CC will often allow the physician to confidently size and count gallstone fragments. In extracorporeal gallstone hithotripsy, our combined experiences indicate that the final determination of a patient’s eligibility for nonsurgical alternatives will be made from the composite data provided by US and

0CC

b. Figure

8.

Size

discrepancy

between

measurements

of barge

(a) Chobecystosonogram shows largest dimension image shows a radiotucent stone with the longest diameter of 15 mm, a significant discrepancy from

stones

obtained

of calculus (arrow) diameter measuring the sonographic

OCG. (b) OCG

at US

and

to be 13 mm. 29 mm and measurements.

a shorter

findings.

The

information

re-

garding cystic duct patency is necessary not only for gallstone ESWL but also for orally administered bile acid therapy. This information is readily available from 0CC. Recently, however, cholecystosonography before and after a fatty meal has been shown to enable accurate assessment of gallbladder function and cystic duct patency (67).

DISTINCTION

BETWEEN

CHOLESTEROL

AND

PIGMENT

STONES The lesterol

has

differentiation stones and

become

between pigment

critical

since

chostones

the

newer

alternatives to elective cholecystectomy are effective only on cholesterol stones. 0CC aids in the determination of stone composition necessary for entry into gallstone ESWL and MTBE contact dissolution protocols as well as eligibility for orally administered bile acid therapy (Fig 9) (68). Features on 0CC images suggestive of cholesterol stones in addition

to areas

b. Figure

9.

therapy.

Importance (a)

two

small

was

not

after stones,

Erect

buoyant

of OCG

but

image CT

(Actigalt; calcified

interpretation

in

radiolucent

appreciated;

ursodiol

accurate

a patient

calculi

was

not

Ciba-Geigy, stone

is intact.

of who

elected

(arrows)

performed.

Summit,

NJ) findings

in

orally

to receive

and (b)

These

OCG

a large

Follow-up

administered oral

bile

bile acid

nonbuoyant

stone.

OCG

obtained

therapy

shows

were

confirmed

image

acid

therapy

shows

Calcified

elimination

rim

8 months

of buoyant

Buoyancy

at surgery.

counting

and

siz-

ing of gallstones can be explained by the superior resolution of the radiographic technique versus US, a tomographic method. Confidence level studies as well as in vitro experirnents have confirmed the superiority of 0CC in the sizing of larger stones and the quantification of multiple small stones or fragments (65,66). In addition to its role as the primary modality in the diagnosis of gallstones, US will be used in the followup of patients during orally adrninisVolume

178

#{149} Number

1

tered bile acid therapy, after methyl tert-butyl ether (MTBE) infusion, and in the examination of patients after

ESWL procedures ing stone fragments

to evaluate remainor possible corn-

plications such as cystic or biliary duct dilatation, focal liver changes, pancreatitis, or gallbladder wall abnormalities. However, 0CC will remain important in the screening of

patients for entry into nonsurgical alternatives stone disease and will mentary

need

to US

the

newer to treat be comple-

in determining

for retreatment

in ESWL

gall-

include

only

stones

sign

tients in facilitating

is the

cholesterol

this 0CC

of radiolucency

the

presence of multiple stones without calcification, a diameter greater than 6 mm, rim calcification, and the layering of floating stones (buoyancy).

is seen

(69).

unreliable

reliable

on

0CC

in only

The

other

sign

35% of pa-

features

individually.

were

Buoyancy

demonstrated more frequently 0CC images than on US scans sumably because of an increase

specific gravity the 0CC agent, stone

to float.

nography

of bile which When

of

images;

is on prein the

produced by allows the cholecystoso-

is performed

in conjunc-

tion with 0CC, buoyancy can be shown at gallbladder US examination (Fig 10) (70). The detection of calcifications in gallstones has also assumed impor-

the

tance

since

none

proto-

agents

are

effective

of the on

chernolytic calcium.

Radiology

Call-

.

55

a.

b.

C.

Figure 10. Buoyancy of cholesterol stones at OCG and chobecystosonography. (a) Initial gallbladder US scan shows multiple stones (arrow) in the dependent segment of gallbladder. (b) OCG image obtained 1 month later for consideration of patient for nonsurgical alternative protocobs shows floating radiobucent stones (arrow) indicative of a cholesterol composition. (c) US scan obtained immediately after OCG shows floating stones (arrow). When gallstone buoyancy is demonstrated either at OCG or cholecystosonography, cholesterol composition of the stones

is ensured.

stones are radiolucent in 80% of cases and are therefore not visible on plain radiographs of the abdomen (71). It has been shown that 86% of these radiolucent stones are composed of cholesterol while 14% are pigment gallstones (72). Of gallstones that are sufficiently calcified to be visible on plain radiographs, two-thirds are composed of pigment and only onethird are composed predominantly of cholesterol. The central type of calcification is often indicative of pigment stones as opposed to the peripheral rim calcification that is frequently seen in cholesterol stones (73). A specific but rarely encountered finding in predominantly cholesterol stones is the “MercedesBenz” sign (Fig 11) (74). These are

Figure

distinctive

tor in predicting

stehlate

radiolucent

areas

resembling the symbol of the German-made automobile in the right upper quadrant due to gas-contain-

ing fissures within fissures result from

gallstones. shrinkage

The of the

cholesterol crystals composing the gallstone and are filled with nitrogen. Neither plain radiographs nor the 0CC images, however, are as sensitive as computed tomographic (CT) scans in distinguishing between cholesterol and pigment stones and in detecting calcification (Fig 12). However, when buoyancy is dernonstrated at 0CC, it appears that CT is superfluous. In vitro and in vivo measurement of CT attenuation appears to be reliable in characterizing gallstone composition (75,76). Whether the significant increase in both cost and radiation exposure with the use of CT is offset by the gain in manage56

#{149} Radiology

11. Mercedes-Benz sign. Gas-fibbed (arrow) within gallstones are shown in this tomogram of a faintly opacified gallbladder, indicating predominant cholesterol fissures

composition

ment

of the

stones.

information

remains

US is of no value tion of gallstone

to be seen.

in the determinacomposition (77,78).

GALLBLADDER FUNCTION A RISK PROGNOSTICATOR The

current

consensus

AS

is that

only

symptomatic gallstones should be treated. The assessment of gallbladder function, as exemplified by visuahization, has been shown to be a fac-

the

risk

ing future complications presence of cholehithiasis information has recently hized in the risk-benefit essary to decide whether

cholecystectorny

(or its newer

natives) is indicated tions of gallstones

to occur patients

of developin the (79). This been utianalysis necelective

the

years

0CC.

of age

Patients

older

in whom

the

was not visualized are more likely to develop

than

those

younger

discovered

at US,

60

gallbladder

four times complications

than

whom the gallbladder ized. If one considers the cy with which gallstones tally

than

60 years was

visual-

high are the

frequeninciden-

informa-

In many respects, 0CC information obtained

gallbladder

nearly twice as frequently in with nonvisualized gallblad-

in

examinaclinical

CONCLUSION

alter-

(80). Comphicahave been shown

ders. Stratification by patient age magnifies the importance of a nonvisualized gallbladder as determined with

tion afforded by the 0CC tion can be of significant prognostic value.

US (the

ability

combines at both

to demon-

strate stones) and radionuclide examinations (the ability to assess cystic duct patency). It is not as sensitive as US in the detection of small stones

and

cannot

be performed

as expedi-

tiously as radionuclide examinations in the prompt diagnosis of cystic duct obstruction; it is not as accurate as CT in the determination of gallstone composition and detection of calcifications. 0CC, however, provides sufficient information regarding cystic

duct tion the

patency

and

gallbladder

func-

and is accurate in determining number and size of stones. January

In 1991

3.

Berk berg

RN, Ferrucci PL, Weissmann

JT,

Fordtran

HS.

JS,

The

Copper-

radiotogi-

cal diagnosis of gallbladder disease: an imaging symposium. Radiology 1981;

4.

5.

141:49-56. Cole WH. Historical features tography: the Carman lecture. 1961; 76:354-375. Graham EA, Cole WH, Copher atization salt

of the

of cholecysRadiology GH.

gallbladder

by

Visu-

the

sodium

of tetrabromophenolphthalein.

JAMA

1924; 82:177-178.

6.

Cole

7.

Am J Surg 1960; 99:206-222. Menees TD, Robinson HC.

WH.

The

story

tration of sodium tein: a preliminary

8.

of cholecystography.

5:211-221. Berk RN, Loeb PM. oral cholecystography. cas J, eds. Radiographic Baltimore:

Oral adminis-

tetrabromophenolphthareport. Radiology Contrast

materials

In: Miller contrast

University

1925;

Park

for

RE, Skuagents.

Press,

1977;

195-221. 0.

9.

Figure 12. Insensitivity of OCG in detection of calcification. (a) Overpenetrated supine OCG image shows radiolucent calculus with no visible calcium rim (arrow). The preliminary KUB radiograph was also unremarkable. (b) CT scan of same patient demonstrates calcium rim

in a cholesterol

stone

Berk

RN.

RN,

Ferrucci

ology agnosis

Oral

of the and

Saunders,

(arrow). 10.

12.

Leopold

Radi-

and bile ducts: Philadelphia:

S.

Observations

of aryltriiodoalkanoic with particular

di-

on a

acid

derivato a new

reference

cholecystographic medium, Tetepaque. AJR 1953; 69:630-637. Jollow DJ, Brodie BB. Mechanisms of drug absorption and of drug solution. Pharmacology Hogben CAM, Schanker LS.

1972; 8:21-32. Tocco DJ, Brodie On the mechanism

intestinal absorption Exp Ther 1959;

Knoefet

PK.

York:

14.

eds.

83-162.

JO, Archer

Radiocontrast

EC.

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Pharma-

125:275-282.

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Lasser

BB, of the

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cot 13.

In: Berk GR,

gallbladder intervention. 1983;

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11.

cholecystography.

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agents.

New

1971.

Pharmacodynamics

media.

Radiot

of biliary

Clin

North

Am

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Gotdberger

LE,

Berk

pharmaceutical

16.

some instances, can be predicted

onstration pensively

the

place

stone composition accurately (ie,

of buoyancy) with

of the

0CC.

and Table

information

“Physicians once considered 0CC to be an uncomplicated radiologic procedure that is simple to perform and easy to interpret. In reality few examinations in radiology require more expertise.” A basic knowledge of the pharmacology of bihiary contrast agents, proper patient preparation,

dern-

inex2 shows

obtained

from 0CC in the current elective management of gallstones. Although many of the treatment methods for

gallstones

that

do not

require

remov-

a! of the gallbladder presently undergoing clinical evaluation may become obsolete with the recent introduction of an endoscopic/surgical modification to remove gallstones (laparoscopic cholecystectomy), the approval by the Food and Drug Administration in 1988 of ursodeoxycholic for clinical use for oral dissolution of cholesterol gallstones will en-

sure continued use of 0CC. The prognostic information regarding

in-

tegrity of the gallbladder wall (ie, function), although not commonly used in the past, may be valid in this era of emphasis on conservative management of gallbladder stones (80,81). As stated by Berk and Leopold (2),

Volume

178

#{149} Number

1

the use of meticulous radiographic techniques, and understanding terpretive

principles

will

ologists

to understand

the

role

0CC in current clinical imaging and management alternatives of nonemergent gallstone disease. Refocused 0CC is still useful. U Acknowledgment: manuscript

We thank

Fran

Shaul

for

Health

and

College

Committee,

of Physicians.

gallbladder.

Ann

Med

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the

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