Oral contrast agents used during CT colonography (CTC) are valuable and may reduce false positive and false negative detections due to stool and residual fluid. Electronic cleansing algorithms are feasible, and oral contrast agents can eliminate the CTC requirement for a clean colon. Recent work shows oral contrast frequently adheres to polyps, with a preference for those with villous histology, a characteristic of advanced polyps. This finding encourages the development of contrast agents that highlight polyps at greatest risk for progression to malignancy. Our review summarizes numerous aspects of oral barium sulfate contrast agents as well as tests to assess adherence and coating ability of the agents, offering arenas to explore and tools for evaluation.
With the coming era of oral contrast-enhanced CT colonography (CTC, or virtual colonoscopy), this is an opportune time to revisit oral barium sulfate contrast agents. As stool and isoattenuating residual fluid are common causes of false negative and false positive detections during CTC, marking colon contents with oral contrast agents may improve the accuracy of CTC ( ). Indeed, studies using oral contrast agents have shown them to be valuable and suggest that they be routinely administered ( ). Electronic cleansing algorithms that remove opacified fluid are feasible and allow for three-dimensional endoluminal imaging of oral contrast−enhanced studies ( ). Oral contrast agents may also eliminate the requirement for a clean colon, as opacified stool and residual fluid can be distinguished either electronically or visually from polyps and normal colonic mucosa ( ).
The use of oral contrast agents to purposefully coat abnormal colonic mucosa during CTC has not previously been a subject of interest. However, recent research shows that oral contrast agents often coat polyps with a preference for those at risk for villous histology, a property of advanced polyps ( ). This finding may allow characterization of colonic mucosa at a level of detail smaller than generally thought possible with CTC.
In order to study oral contrast agents and their role as general opacification or targeted coating materials, it is necessary to review the complex formulation of their contents and address why they coat colonic mucosa. These questions have not been addressed for some time but have become relevant again with the use of contrast-enhanced CTC. Due to proprietary information restrictions, little is known about the exact ingredients and makeup of current oral contrast agents, leaving many questions to be answered by future research. Our review summarizes various aspects of oral barium sulfate preparations and provides possible arenas to explore when developing contrast agents that will preferentially adhere to polyps or normal mucosa.
Oral barium sulfate solution basics
Available Formulations
Oral barium sulfate contrast agents are available in powder or liquid forms; powders need to be reconstituted with water and liquids may need to be diluted. Barium sulfate agents are superior to water-soluble contrast media in their ability to define the mucosal surface and their resistance to dilution ( ). As the pH of the gastrointestinal tract may range from 0.8 to 8.0, different formulas have been created to optimize coating for specific studies ( ). Double contrast barium enemas (DCBEs, the study that approximates coating seen during CTC) usually use concentrations of barium sulfate in the range of 50−61% w/w or 80−100% w/v ( ).
There are many brands of barium sulfate available for clinical use. The major U.S. manufacturers are E-Z-Em (Lake Success, NY; http://www.ezem.com/ ) and Tyco Healthcare (Mansfield, MA; Mallinckrodt subsidiary and Lafayette products, Hazelwood, MO; http://imaging.mallinckrodt.com/ ).
Labeling
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Purpose
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Table 1
Properties of barium sulfate preparations and their clinical relevance.
Properties Clinical Relevance Barium sulfate particles Size Smaller particles may improve coating Charge Mostly indeterminate—additives determine charge of suspensions Additives Deflocculation agents Improve uniformity and quality of coat Suspending agents Improve shelf-life; may increase viscosity Dispersing agents Improve mixing with colonic contents and mucus; may improve coating Wetting agents Enhance film formation; improve coating Antidrying agents Improve suspension of barium sulfate particles Antifoaming agents Prevent bubble formation; improve coating quality Flavoring agents Improve taste and patient acceptability Magnesium Improves coating Physical characteristics Plasticity Plastic substances (those that require shear stress to initiate flow, then stress is proportional to shear) preferred to pseudo-plastic ones (those that flow immediately, then change in viscosity is inversely proportional to change in shear stress) Viscosity/density High viscosity/medium density or low viscosity/high density preferred Thixotrophy Increased thixotrophy (tendency to stiffen if undisturbed) may improve coating
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Barium sulphate particles
Particle Size
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Particle Charge
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Additives
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Deflocculation Agents
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Suspending Agents
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Dispersing Agents
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Wetting Agents
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Antidrying Agents
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Antifoaming Agents
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Flavoring Agents
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Magnesium
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Physical characteristics of barium sulphate preparations
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Plasticity
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Viscosity and Density
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Thixotrophy
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Coating and adhesion tests
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In Vitro Testing
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Tissue Sample Testing
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Animal Models
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In Vivo Testing
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Table 2
In vivo barium sulfate mucosal coating comparison studies in patients.
Study Preparations Used Evaluation Results Anderson, 1980 (35) ⁎
One observer rates the demonstration of areae gastricae: satisfactory, poor, or unacceptable A, B: large majority satisfactory (0.94 (49 satisfactory, 3 poor), 0.93 (54 satisfactory, 4 poor)) C, D: satisfactory (0.68 (36 satisfactory, 17 poor), 0.61 (30 satisfactory, 19 poor) E: unacceptable, stopped after 9 patients Bray, 1993 (42) †
Two observers rate coating on a 5-point scale for five colonic segments, results averaged Premixed suspension (B) had significantly better coating of the mucosa in all areas of the colon Cittadini, 2001 (46) †
Three radiologists rate mucosal coating on a 0−4 scale for three colonic segments, worst score per colon used Addition of Mg outperforms Na in all groups with equal viscosities; G2 + Mg with best coating overall Cittadini, 1999 (47) †
Three radiologists rate mucosal coating on a 0−4 scale for three colonic segments, worst score per colon used Coating was better in subjects with MgSO 4 preparations Cittadini, 1999 (51) †
Two radiologists rate mucosal coating on a 0−4 scale for three colonic segments, worst score per colon used Sennosides + Mg gave best mucosal coating Moreton, 1950 (52) †
Unknown person(s) rate mucosal coating satisfactory or unsatisfactory I, II: unsuitable for double contrast barium enema III, IV: “satisfactory” coating
Manufacturers:
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Iodinated contrast agents
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Future directions
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Acknowledgment
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