Bilary Contrast Agents an Introduction


Oral cholangiography
The development of radiology of the biliary tract has been punctuated at intervals by advances of prime importance. The first of these was the development of oral cholecystography. This closely followed Graham and Cole's (1924) initial opacification of the gallbladder using intravenous sodium tetrabrom-phenolphthalein.

Subsequent improvements in the radiopacity tolerance of oral contrast media did not alter the nature of the test. For success this depends adequate absorption of the oral medium from the intestine, excretion from the liver with the bile, patency of the cystic duct and finally adequate concentration the gallbladder. This requires 10 to 12 hours for completion.

1. Adequate absorption of the medium from the gut
Failure can be attributed to non-absorption in cases of unsuspected achalasia of the cardia or pyloric stenosis both of which effectively prevent the medium reaching the small bowel. In addition, the absorption of oral media, such as Telepaque may be impaired in the absence of bile salts and therefore the instruction to avoid fat before ingesting oral media is mistaken. All oral and venous media are transported in the blood bound plasma albumen which reduces the chance of excretion. (Berk and Loeb, 1976).

2. Excretion from the liver with the bile
Technical failure can occur in cases of unsuspected cirrhosis of the liver or other causes of liver insufficiency. Obviously in cases of jaundice the chances of a such examination are minimal.
Like Bilirubin, oral media are converted t excreted as soluble glucuronides conjugated in transit while intravenous media (Biligrafin, Biligram excreted unchanged (Berk and Loeb, 1976).

3. Patency of the cystic duct
A blocked cystic duct is the commonest cause of repeated failure to obtain a shadow after oral cholecystography and always indicates a pathological gallbladder. The obstruction in the duct is commonly due to stones but occasionally to an inflammatory stricture.

4. Adequate concentration of medium in the gallbladder. As the concentration of oral contrast media in the hepatic bile is usually too low to cast a shadow, no image of the gallbladder will show until its contents are concentrated. This requires both time and a normal gallbladder mucosa. By taking the oral contrast medium overnight, full opportunity is given to the gallbladder to fill, retain and concentrate its contents; especially important also in this respect is the entero-hepatic recirculation which all oral media normally undergo. This is in distinct contrast to intravenous media which are not reabsorbed from the gut.

Modern oral contrast media. The media in common use today are shown in the table below, together with the manufacturing laboratory and the chemical composition. Modern media depend for their radio-opacity on 3 iodine atoms in the molecule and they contain between 60 per cent and 68 per cent iodine by weight. The dosage is usually 3 g taken at night 12 hours before radiography, although the amount can be increased in large patients.

Advances in oral technique have been the introduction of sodium ipodate (Biloptin) and calcium ipodate (SoluBiloptin). These media, like intravenous compounds, are concentrated sufficiently by the liver to be demonstrable in the hepatic bile. As a result, by using the medium at night in the usual way but supplementing this with another dose by mouth 2 hours before the examination, the common duct can be visualized in a high proportion of cases before the gallbladder contracts and even if it does not fill.

The following advantages of this technique over others therefore became evident :

1. The incidence of non-opacifying gallbladders is lower, as visualization no longer depends on gallbladder concentrating power alone-a patent gallbladder with a damaged mucosa will now show.
2. Delineation of the hepatic bile flowing down the common duct indicates adequate absorption and excretion; a non-opacifying gallbladder in these circumstances must be due to cystic duct obstruction and is, therefore, unquestionably pathological. Confirmation by repeat oral or intravenous techniques is consequently rendered superfluous.
3. The calibre of the duct, if excessive, will indicate that it is partially obstructed; in addition, it produces a record of calibre for possible future use if symptoms recur post-operatively.

Toxicity. 
In general, toxic reactions from modern oral biliary contrast agents are slight  and consist of mild headache,  nausea, diarrhoea and sometimes dysuria.
Undue sensitivity, however, does occasionally occur and is related to the chemical structure of the compound. Such allergic reactions may be accompanied by urticaria, oedema of the face, eyes and rarely the larynx. if reaction occurs, a different chemical compound will usually be satisfactory. There is also a relation between the degree of protein binding in the blood and the toxicity of the contrast agents; for example, intravenous Biligrafin is the most highly bound and also the most toxic of the biliary media (Berk and Loeb, 1976).

Intravenous cholangiography
The next advance of importance was the introduction of intravenous cholangiography and cholecystography (Biligrafin) in 1953. (A newer intravenous medium, Biligram, is referred to below.) For the first time opacified bile could be observed in transit down the common duct whether a gallbladder was present or not; this was and remains the most important role of i.v. cholangiography. In addition it offered an alternative technique of examination, particularly important in cases of nonopacifying gallbladders at oral cholecystograms. Studies with this medium confirmed that these non-opacifying gallbladders were pathological in the majority of cases due to cystic duct obstruction (usually by stone) but they were occasionally patent. Reports of normal intravenous examinations following upon failed oral cholecystograms appeared (Stenhouse, 1958) which confirmed and approximated to the normal surgical findings quoted above. Less common was the converse of this phenomenon, i.e. failure of a normal gallbladder to fill on the intravenous examination whereas it filled and concentrated normally on the oral cholecystogram. A similar parallel series using surgery as the control of normality showed 6 out of 46 non-filling gallbladders over a two hour period with intravenous iodipamide (Biligrafin) were normal (13 per cent) (Wise, Johnston and Salzman, 1957).

Technique. 
Owing to the fact that the methyl glucamine ioglycamate molecule is large and contains only 48 per cent iodine, the radio-opacity of the medium in the common duct is not great. Consequently films should be taken with a small cone, a low K. V. technique and with the patient slightly prone oblique to cast the duct clear of the spine.

It is obviously important to obtain a maximum concentration of the intravenous medium in the bile Experimental work has shown that this is best achieved by slow administration over 10-15 minutes either by syringe or by a drip technique in saline. This may increase the concentration by increasing the proportion bound to plasma albumen (so reducing the renal excretion) resulting in a 10 per cent improvement in the density of the image.

In addition, all intravenous cholangiographic media are cholagogues; by reducing the bile flow before the examination to a minimum, relatively low dose cholangiography (with consequently reduced toxicity) is feasible. Bile salts have a similar choleretic effect and the enterohepatic recirculation of these can be reduced to a minimum by fasting, so reducing the bile flow; consequently the examination should be performed in a fasting state (Berk and Loeb, 1976).

The medium appears in the duct 15-20 minutes after injection and begins to fall off' in density after 1 hour. Better results are obtained if the patient is left on the table between exposures. Gallbladder filling commences early in many cases, but occasionally is delayed; most gallbladders will fill in 2 hours.

Biliary Contrast Agents

Registered name Manufacturer Chemical Name

Telepaque Bayer Iodopanoic Acid
Biloptin Schering Sodium Ipodate
Solu-Biloptin Schering Calcium Ipodate
Biligram Schering Meglumine Ioglycamate

From
Sutton, D,1980 A textbook of Radiology & Imaging, Churchill Livingstone, London