Negative GI Contrast Agents

Negative GI contrast materials can be divided into three categories: diamagnetic agents, superparamagnetic agents, and perfluorochemicals.

Diamagnetic Contrast Agents

Two diamagnetic agents have been tested for use as a negative GI contrast agent. The first was a combination of clay minerals found in a popular antidiarrheal medication, Kaopectate. This mixture of kaolin and bentonite is thought to facilitate the relaxation rate of protons in water molecules. The water molecules next to the surface of the clay are continually exchanging position with molecules away from the surface resulting in phase dispersion that also causes loss of signal. When used in volunteers, this mixture causes loss of signal in the stomach and duodenum resulting in improved visualization of the pancreas. Distribution in the small bowel is reported to be nonuniform.
The second diamagnetic contrast agent causing loss of signal in the bowel is barium sulfate suspension. The decrease in signal seen is a result of two processes: 1) replacement of water protons by barium; and 2) magnetic susceptibility effects around the barium particals. Testing of a conventional barium sulfate suspension (60% wt/wt) in volunteers and patients gives encouraging results. Our in vitro and volunteer studies at higher concentrations of barium sulfate show that the 170% to 220% wt/vl suspensions give greater loss of signal than the original barium tested. The loss of signal from barium sulfate suspensions does not match that seen with superparamagnetic iron oxide described below, however barium suspensions are currently readily available and probably will be much less expensive.

Superparamagnetic Contrast Agents

There are several preparations of superparamagnetic agents can be used as oral MRI contrast agents. These include magnetite albumin microspheres, oral magnetic particles (Nycomed A/S, Oslo, Norway), and superparamagnetic iron oxide (AMI121, Advanced Magnetics, Cambridge, Mass.). These three contain small iron oxide crystals approximately 250 to 350 angstroms in diameter and are mixtures of Fe2O3 and Fe3O4. The small size of the crystals contributes to their large magnetic moment without significant residual magnetization after removal from the magnetic field, i.e., they are superparamagnetic, not ferromagnetic. These crystals are embedded in an inert material, albumin matrix in the first case, a monodispersed polymer in the second, and an inert silicon polymer in the third. The inert materials reduce absorption and therefore, toxicity from the iron. They also help to suspend the particles in solution.
Marked loss of signal in the stomach and small bowel results in excellent visualization of the pancreas, anterior renal margins and para-aortic regions. Decrease in the phase encoded artifacts from respiratory and peristaltic motion of the stomach and small bowel are noted. At certain concentrations and volumes, metallic artifacts are seen in the distal small bowel and colon on delayed imaging. These may be related to settling and concentration of the particles. Optimization of the dose of contrast agent and addition of more suspending agents may overcome this problem. Agents such as cellulose or polyethylene glycol may be added to enhance relaxation and thereby allow reduction in the concentration of iron oxide needed. This may reduce the artifacts.

Perfluorochemicals

Diamagnetic and paramagnetic effects are not the only mechanisms for reducing signal in the bowel. The absence of mobile protons will give this effect as seen with barium sulfate suspended in D2O, carbon dioxide, and perfluorochemicals. CO2 from effervescent granules is moderately well tolerated by patients but shows inhomogeneous distribution in the small bowel, and requires the use of glucagon to decrease peristalsis.
Perfluorochemicals are organic compounds in which the protons are replaced by fluorine. This results in an absence of signal in the bowel. Perfluoroctylbromide(PFOB)(C8F17Br) is the only perfluorochemical that has been investigated for oral use in humans to date. It is commercially available now as perflubron (Imagent GI, Alliance), but at high cost ($200 per 200cc bottle). Potential advantages are a rapid transit through the small bowel because of its low surface tension, the lack of taste or odor making it palatable, and the absence of any known side effects. PFOB is immiscible as are all perfluorochemicals that are in their pure or "neat" state. This may be an advantage because PFOB cannot be diluted by bowel contents, however, miscible agents that mix with fluid in the bowel may give more uniform filling of the GI tract. Emulsifying PFOB, as is done for intravascular use of perfluorochemicals, may overcome this potential problem.