Gastrointestinal MRI contrast agents
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Gastrointestinal MRI contrast agents may be helpful in certain clinical scenarios in distinguishing bowel from intra-abdominal masses and normal organs. The contrast agents can be divided into positive agents (appearing bright on MRI) or negative agents (appearing dark on MRI).
Positive contrast agents
Positive GI contrast agents can be divided into three categories:
- paramagnetic agents (e.g. Gd-DTPA solutions)
- short T1-relaxation agents (e.g. mineral oil)
- combination agents containing both "1." and "2."
Proposed paramagnetic, positive GI contrast agents include ferric chloride, ferric ammonium citrate, and gadolinium-DTPA (with and without mannitol). Paramagnetic materials cause both T1 and T2 shortening.
At low concentrations used for bowel opacification, the T1 shortening dominates the signal intensity. This results in high intensity on T1-weighted, T2-weighted and gradient echo images. At high concentrations, T2 shortening causes decreased signal in all but very short echo sequences. This resembles the effect seen with superparamagnetic iron oxide (see negative GI contrast agents). At intermediate concentrations, a mixture of T1 and T2 shortening results in increased signal on T1-weighted images and decreased signal on T2-weighted images.
Ferric ammonium citrate and Gd-DTPA with mannitol are safe and effective in humans, but both have minor side effects. Ferric iron can cause teeth staining, gastric irritation, nausea, diarrhea, and constipation. Mannitol can cause nausea, vomiting, and diarrhea. Gd-DTPA without mannitol is well tolerated but usually fails to opacify the entire small bowel. It also needs to be buffered when used orally since this chelate is not very stable at the low pH found in the stomach 1.
Short T1-relaxation agents
Short T1 relaxation time GI contrast agents include mineral oil, oil emulsions, and sucrose polyester. In these materials, protons contained in -CH2- groups relax at a faster rate than those in water resulting in a short T1 time. This gives a bright signal in the bowel on T1-weighted sequences. Of these materials only oil emulsions have been used successfully in humans. These are palatable and produce homogeneous opacification of the stomach and small bowel, but are absorbed in the distal small bowel and fail to fill the colon. This is circumvented by using a contrast enema when the colon must be better visualized.
A novel approach to retrograde opacification of the colon has been shown in rats with sucrose polyester, a non-absorbable fat substitute, but no human trials for this use have been done 2.
Combination contrast agents
Combinations of oil emulsion and paramagnetic substances may be used as bowel contrast agents. These include an emulsion-containing corn oil and ferric ammonium citrate, and an emulsion-containing baby formula with ferrous sulfate. These are palatable mixtures that distribute uniformly in the bowel, however signal is lost in the distal small bowel in adults, because of absorption of both the oil and the iron. Unlike in adults, the faster transit through the small bowel in infants delivers bright contrast to the colon. The advantage of this combination over oil emulsions alone is the enhancement of signal on T1-weighted and especially T2-weighted images.
Negative contrast agents
Negative GI contrast materials can be divided into three categories:
- diamagnetic agents (see diamagnetism)
- superparamagnetic agents (see superparamagnetism)
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 antidiarrhoeal 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 3-4.
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:
- replacement of water protons by barium
- magnetic susceptibility effects around the barium particles
Testing of a conventional barium sulfate suspension (60% wt/wt) in volunteers and patients gives encouraging results. 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 3-4.
Superparamagnetic contrast agents
There are several preparations of superparamagnetic agents that can be used as oral MRI contrast agents. These include magnetite albumin microspheres, oral magnetic particles, and superparamagnetic iron oxides. These 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 5.
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 5.
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. Perfluoroctyl bromide (C8BrF17), also known as PFOB, is the only perfluorochemical that has been investigated for oral use in humans to date. It is commercially available now as Imagent but at high cost. 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.
Positive vs negative contrast agents
The question of which type of contrast enhancement of the bowel is the best, positive or negative, is still debated. We may find a positive or negative oral contrast agent better depending on the specific organ or disease suspected and the pulse sequence used.
Advantages of positive agents
An advantage of positive oral contrast agents is the availability of several of these materials at this time. These include ferric ammonium citrate, pediatric formula, and homemade oil emulsions. Positive agents are also inexpensive (except for gadolinium solutions) and are safe to use.
Disadvantages of positive agents
Two disadvantages of positive oral contrast agents are ghosting artifacts because of respiratory and peristaltic motion, and loss of signal from dilution with secretions and retained fluid in the bowel. One method of reducing ghosting artifacts is to use a pharmaceutical, such as hyoscine-N-butylbromide or glucagon, to reduce bowel motion. This increases the invasiveness of the procedure. Other methods include the use of breath-holding pulse sequences and first order flow compensation.
Dilution of positive contrast agents occurs in the upper GI tract if they are miscible with water because of gastrointestinal secretions. This allows for the use of a small dose, but will cause loss of signal intensity as the concentration decreases. Immiscible positive agents using oils, especially non-absorbable ones, will not experience the loss of signal with dilution. They will probably require a larger volume to replace any residual bowel contents.
Another disadvantage of a positive oral contrast agent is the possibility of residual material in the bowel simulating a mass when surrounded by bright signal. The opposite is also true. A bright mass (such as a lipoma) might be obscured by the contrast agent.
Advantages of negative agents
Advantages of negative oral contrast materials are several. The lack of signal in the bowel removes a source of ghosting artifacts from spin echo sequences that may be present with positive agents. The loss of signal is fairly independent of concentration of superparamagnetic iron oxide suspensions on spin echo sequences so that dilution should not be a problem. The perfluorochemicals are immiscible with water and will not encounter dilution problems either.
Disadvantages of negative agents
Disadvantages of negative oral contrast materials include their high cost and lack of general availability (except for CO2 and barium sulfate), and limited evaluations of safety on large number of patients. The expense may decrease with greater use of these contrast materials and with competition between manufacturers. Metallic artifacts are seen when iron oxide concentrations, ideal for spin echo sequences, are used with gradient echo sequences. This is because gradient echo sequences have greater sensitivity to magnetic field inhomogeneity. Also there were some metallic artifacts seen in the colon on delayed (24 hour) imaging with the iron oxide preparations that probably can be eliminated as discussed above.
Lack of a fat plane between the negative contrast-filled bowel and low signal intensity organs may make it difficult to distinguish normal contours. An example of this is the plane between the stomach and the pancreas on T2-weighted sequences. The majority of pathology appears bright on T2-weighted sequences and should be seen, however.
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