Radiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Luboldt, W.
Right arrow Articles by Debatin, J. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luboldt, W.
Right arrow Articles by Debatin, J. F.
(Radiology. 1999;212:265-269.)
© RSNA, 1999

Technical Developments

MR Colonography: Optimized Enema Composition1

Wolfgang Luboldt, MD, Johannes M. Frohlich, PhD, Nicole Schneider, MD, Dominik Weishaupt, MD, Franziska Landolt, MSc and Jorg F. Debatin, MD

1 From the Institute of Diagnostic Radiology, University Hospital Zurich, Ramistrasse 100, CH-8091 Zurich, Switzerland. Received May 27, 1998; revision requested August 5; revision received September 10; accepted December 16. Supported in part by German Research Foundation stipend Lu 687/1-1. Address reprint requests to J.F.D. (e-mail: debatin@drnr.usz.ch).


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Manganese chloride, iron glycerophosphate, and cellulose additive were assessed as base materials for use in a T1-shortening single contrast enema for magnetic resonance (MR) colonography. Contrast-to-noise ratios (CNRs) were compared to those with the standard 10 mmol/L gadolinium–based enema. On T1-weighted three-dimensional gradient-recalled-echo images, CNRs with the iron glycerophosphate enema exceeded those with the manganese- and gadolinium-based enemas. Use of an additive of 0.8% wt/wt cellulose was found to be practicable as it increased viscosity sufficiently without altering CNR. The gadolinium-based enema can be replaced with an iron glycerophosphate enema to render MR colonography less costly.

Index terms: Colon, MR, 75.121412, 75.121419, 75.12143 • Gadolinium • Iron • Magnetic resonance (MR), contrast agents, 75.121412, 75.121419, 75.12143 • Magnetic resonance (MR), contrast enhancement, 75.12143 • Manganese


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Magnetic resonance (MR) colonography combines the application of a rectal enema containing paramagnetic contrast agent with breath-hold, T1-weighted, high-spatial-resolution, three-dimensional (3D) imaging and heavily T2-weighted, two-dimensional (2D), single-shot, spin-echo (SE) imaging (1). Beyond being biocompatible, the enema used at MR colonography needs to fulfill MR signal intensity (SI) and mechanical requirements. For reconstruction of endoscopic views, the enema should be homogeneously bright on T1-weighted, 3D, gradient-recalled-echo (GRE) images and homogeneously dark on T2-weighted images for better depiction of pathologic conditions contained within the colonic wall. In addition, the enema needs to homogeneously fill and distend the colon. These mechanical properties are mainly dependent on the viscosity of the enema.

Presently, an enema with 10 mmol of gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Wayne, NJ) per liter of water is used for MR colonography. Although it fulfills the SI requirements, the low viscosity induces backflow into the small bowel, which complicates subsequent analysis and reduces colonic distention. More important however, the enema has a volume of up to 2,000 mL and thus requires use of as much as 40 mL of a 0.5 mol/L paramagnetic contrast agent formulation. The associated cost is high, which negatively effects consideration of MR colonography as a screening alternative for colonic polyps.

The purpose of this study was to identify a less costly, more viscous enema with SI characteristics similar to those with the 10 mmol/L gadopentetate dimeglumine and water enema currently employed.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
MR Imaging
All imaging was performed on a 1.5-T system (Signa Acuspot; GE Medical Systems, Milwaukee, Wis). To ensure a sufficiently large field of view to cover the entire colon, the body coil was used for signal transmission and reception. Two sequences were employed: 3D spoiled GRE (repetition time msec/echo time msec = 4.7/2, 45° flip angle, 0.5 signals acquired, 62.5-kHz bandwidth, 382 x 192 matrix, 40 x 40-cm field of view, 2.4-mm section thickness) and 2D single-shot fast SE (65-msec echo time, 31.3-kHz bandwidth, 256 x 192 matrix, 40 x 40-cm field of view, 6-mm section thickness).

Assessment of New Contrast Media
Two agents—manganese chloride and iron glycerophosphate—were assessed as possible replacements for gadopentetate dimeglumine. Water-based dilution series with each agent and with gadopentetate dimeglumine were imaged with the 3D spoiled GRE and 2D single-shot fast SE sequences. In addition, a water-dilution series with iron glycerophosphate and 600 mg of manganese chloride was imaged to determine possible synergistic effects with the two substances. On the basis of SI data acquired on 3D spoiled GRE images, the concentration with which the maximum SI was achieved was determined with a finely incremented dilution series. SI-concentration curves were obtained for each of the four evaluated contrast media.

The contrast media that provided the maximum contrast-to-noise ratio (CNR) on the 3D spoiled GRE images was used at the optimum concentration to fill the colon of three anesthetized pigs. The experiments were conducted in accordance with state regulations governing animal experiments. The colon was imaged with both the 3D spoiled GRE and 2D single-shot fast SE sequences. To determine CNR, SI characteristics of the contrast agent–filled colonic lumen were evaluated relative to the colonic wall and surrounding structures. Additionally, three colonic specimens exposed to the enema were obtained for histologic examination of iron uptake with Prussian blue staining.

Optimization of Enema Viscosity
Cellulose was added to enhance the mechanical properties of the enema by increasing its viscosity. In an initial step, the maximum additive of cellulose was determined that allowed passage of the mixture through the enema tip at 1.5 m of hydrostatic pressure. With this maximum cellulose concentration as a baseline, the enema viscosity was titrated for MR colonography by means of progressive dilution with water until complete colonic filling at 1.5-m hydrostatic pressure was possible.

Dilution experiments were performed in six patients (four men and two women; age range, 53–72 years; mean age, 61 years) undergoing MR colonography in a larger study designed to determine the diagnostic performance of MR colonography in the detection of colonic masses. This study had been approved by the local ethics committee, and written informed consent was obtained from all patients. The patients had undergone colonic preparation for subsequent conventional colonoscopy. Colonic filling was monitored with a non–section-selective 2D spoiled GRE acquisition collecting one image every second. The acquired images permitted assessment of colonic distention and reflux into the small bowel.

To determine the influence on SI characteristics of the cellulose additive in its previously optimized concentration, the gadopentetate dimeglumine and iron glycerophosphate dilution series were repeated with and without the cellulose additive, with the 3D spoiled GRE sequence. The ratio of the resultant SIs with and SIs without cellulose (SIwith/SIwithout) were plotted against the concentrations of gadopentetate dimeglumine and iron glycerophosphate. The paired Student t test was used to assess statistically significant differences in the collected data sets.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
On the T1-weighted 3D spoiled GRE images, both manganese chloride and iron glycerophosphate resulted in an initial concentration-dependent increase in SI followed by an eventual decrease in SI as T2-shortening effects began to dominate T1 effects with increased concentrations (Fig 1). The highest SI was achieved with the iron glycerophosphate and water solution at a concentration of 45 mmol/L, which corresponds to an iron load of 28 g/L. Manganese chloride solutions were associated with lower SI values. Maximum SI was observed with a concentration of 5 mmol/L, which corresponds to a manganese load of 1 g/L. The combination of manganese chloride and iron glycerophosphate showed a synergistic effect as evidenced by SI values that exceeded those with only iron glycerophosphate up to a concentration of 15 mmol/L of iron glycerophosphate (Fig 1). Beyond 15 mmol/L, iron glycerophosphate provided SI values higher than the combination of iron glycerophosphate and manganese chloride. Results with the gadopentetate dimeglumine dilution series revealed a maximum SI at a concentration of 23 mmol/L. The maximum gadopentetate dimeglumine value (SI, 1,932) exceeded values with manganese chloride (SI, 640) but remained lower than the maximum value with iron glycerophosphate (SI, 2,078).



View larger version (19K):
[in this window]
[in a new window]
  		Figure 1. For T1-weighted 3D spoiled GRE images, graph plots SIs relative to dilution series of manganese chloride (Mn), iron glycerophosphate (Fe), manganese chloride and iron glycerophosphate [Fe + Mn (600 mg/l)], or gadopentetate dimeglumine (Gd). In all cases, an initial SI increase is followed by an eventual SI decrease. This appearance reflects the rising T2-shortening effect of these substances as their concentration is increased. The highest maximum was measured with iron glycerophosphate.

 
In pigs, the 45 mmol/L iron glycerophosphate solution provided homogeneously high SI within the colonic lumen on the T1-weighted 3D spoiled GRE images (Fig 2a), which permitted reconstruction of virtual endoscopic images. The mean for CNRs of the colonic lumen relative to surrounding structures was 48 ± 5 (SD). On T2-weighted 2D singleshot fast SE images, the colonic lumen was homogeneously dark, which permitted easy delineation of the hyperintense colonic wall (Fig 2b). The means for CNRs of the colonic wall relative to the colonic lumen or surrounding structures were 21 ± 3 and 10 ± 4, respectively. Histologic analysis of the colonic specimen revealed no evidence of iron uptake into the colonic mucosal cells.



View larger version (140K):
[in this window]
[in a new window]
  		Figure 2a. Coronal (a) 3D spoiled GRE and (b) 2D single-shot fast SE images of the colon after rectal administration of a highly concentrated (28 g/L) iron glycerophosphate enema to a pig. The colonic lumen is bright in a. Even at this high concentration, iron glycerophosphate caused no artifacts. Since the colon of the pig was artificially perforated, the T1-shortening iron glycerophosphate can also be identified within the peritoneal cavity (arrows in a). In b, the colonic lumen is dark. Having inherently high SI on T2-weighted images, the colonic wall (arrowheads) is clearly delineated from the colonic lumen and surrounding structures.

 


View larger version (156K):
[in this window]
[in a new window]
  		Figure 2b. Coronal (a) 3D spoiled GRE and (b) 2D single-shot fast SE images of the colon after rectal administration of a highly concentrated (28 g/L) iron glycerophosphate enema to a pig. The colonic lumen is bright in a. Even at this high concentration, iron glycerophosphate caused no artifacts. Since the colon of the pig was artificially perforated, the T1-shortening iron glycerophosphate can also be identified within the peritoneal cavity (arrows in a). In b, the colonic lumen is dark. Having inherently high SI on T2-weighted images, the colonic wall (arrowheads) is clearly delineated from the colonic lumen and surrounding structures.

 
The cellulose additive beyond 2% wt/wt precluded passage through the enema tip. To ensure easy filling of the entire colon under in vivo conditions, the cellulose additive was lowered to 0.8% wt/wt (Fig 3). At this concentration, there was no reflux noted in any of the six patients. The addition of cellulose at this concentration had no effect on the SI characteristics on 3D spoiled GRE images for either the gadopentetate dimeglumine or iron glycerophosphate dilution series (Fig 4). The paired Student t test revealed no statistically significant differences in SI (P > .5).



View larger version (117K):
[in this window]
[in a new window]
  		Figure 3. MR image of colonic filling permits assessment of colonic distention and reflux into the small bowel. The additive of cellulose prevented reflux of contrast agent into the small bowel in all six patients and resulted in good colonic distention.

 


View larger version (14K):
[in this window]
[in a new window]
  		Figure 4. For T1-weighted 3D spoiled GRE images, graph plots the ratio of SIs obtained with and SIs obtained without the addition of 0.8% wt/wt cellulose depending on the concentration of gadopentetate dimeglumine (Gd) or iron glycerophosphate (Fe). Cellulose had no measurable influence on SIs.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The potential benefits of colonic polyp screening are well documented (2). Recently, we reported promising results with MR colonography (3). Although the cost of MR colonography depends on the content of the enema, its performance depends on the intraluminal SI and distention of the colon. The cost of MR colonography has been rather high, which predominantly reflects the use of as much as 40 mL of gadopentetate dimeglumine as the contrast agent for the enema. Findings in this study demonstrate that the enema can be optimized to dramatically lower the overall cost of an MR colonographic examination.

Presently, the amount of gadopentetate dimeglumine required for optimum contrast on both T1-weighted 3D spoiled GRE and T2-weighted 2D single-shot fast SE images represents a cost factor that would preclude use of MR colonography for screening purposes. Since the contrast agent is administered rectally and not intravenously, there is a considerably wider latitude regarding tolerance and safety of agents. We evaluated two considerably less expensive agents with known T1- and T2-shortening effects as possible alternatives to gadopentetate dimeglumine: manganese chloride and iron glycerophosphate. Manganese was chosen as it is the substance responsible for the T1-shortening effects inherent in blueberry juice (4). Manganese chloride provided a maximum SI (SI, 640) that was 41% of that achieved with gadopentetate dimeglumine (SI, 1,560) at the 10 mmol/L concentration (Fig 1). This cannot be considered sufficient for MR colonography.

Subsequently, iron was tested in its most tolerable form as iron glycerophosphate (5). SI values achieved with iron glycerophosphate were far higher than those associated with manganese chloride and even exceeded those with gadopentetate dimeglumine (Fig 1). Maximum SI values were seen at a concentration of 45 mmol/L, which corresponds to an iron load of 28 g/L. In an attempt to lower the concentration of iron glycerophosphate, manganese chloride was added. The amount of manganese chloride added corresponded to the concentration associated with 87% (SI, 558) of the maximum SI increase in the manganese chloride dilution series (SI, 640). Indeed, the addition of manganese chloride to iron glycerophosphate resulted in higher SI values at lower concentrations. At higher concentrations, the combination reached a maximum SI value of 75% (SI, 1,560) of the maximum SI achieved with iron glycerophosphate alone (SI, 2,078) (Fig 1).

The in vivo imaging characteristics of iron glycerophosphate are favorable for MR colonography. At a concentration of 45 mmol/L, the enema was displayed as homogeneously bright on T1-weighted 3D spoiled GRE images and totally dark on T2-weighted 2D single-shot fast SE images (Fig 2). The visual impressions are corroborated by the high CNRs. In contrast to superparamagnetic iron oxide, which requires matching with diamagnetic barium sulfate particles to avoid susceptibility artifacts (6,7), images obtained with iron glycerophosphate depicted no artifacts up to the tested concentration of 45 mmol/L (Fig 2).

Iron glycerophosphate appears to be a safe agent. In fact, it has been used in high doses without relevant side effects in pediatric populations (8). It is poorly absorbed when administered orally (9,10). Although conclusive data are not available, it is not likely to cause any side effect if administered rectally. As was also confirmed in our study, there is no measurable resorption of this physiologic iron compound in the colon (11). It is conceivable, however, that iron could be resorbed if reflux occurs far into the proximal small bowel. Even if such an extensive reflux were to occur, the transient nature of the iron present in the small bowel would obviate any serious imbalance in iron metabolism. As an additional safeguard, iron could be embedded in macromolecules (iron-dextran, iron-cellulose) that are not resorbed. In this manner, the potential toxicity would be reduced as the viscosity increased.

Similar to double contrast barium enema examination (12,13), accurate assessment of the colonic lumen with MR colonography mandates adequate colonic distention (3). Beyond the administration of antiperistaltic, distention is dependent on the viscosity of the enema. Currently, the enema used at MR colonography consists mainly of water, which results in quick passage of enema fluid through the ileocecal valve into the small bowel in a vast majority of patients. Increases in viscosity must, however, be balanced against the need for easy and fast filling of the colon, particularly in view of limitations regarding usable hydrostatic pressure. Although results of in vitro experiments identified a 2% wt/wt cellulose additive as maximum, results of in vivo evaluations in six patients demonstrated a cellulose additive beyond 0.8% wt/wt to be impracticable. At this concentration, there was no reflux of contrast material into the small bowel and, consequently, distention was good (Fig 3). Results of in vitro experiments showed that the addition of cellulose to the enema did not have any measurable effect on SIs on 3D spoiled GRE images (Fig 4).

Iron glycerophosphate seems to be a feasible alternative to gadopentetate dimeglumine as a contrast enema in MR colonography. Before any clinical use, more safety data need to be collected (eg, by means of radiolabeling techniques with the radioactive isotope iron-59 instead of iron-56 [14]). A relative price difference of a factor of approximately 25 in conjunction with slightly better SI characteristics makes this a worthwhile endeavor. Even though MR colonography may become less expensive with the use of iron glycerophosphate, a cost analysis of MR colonography compared with other modalities, such as barium enema examination or colonoscopy, will need to be performed.


   Footnotes
 
Abbreviations: CNR = contrast-to-noise ratio GRE = gradient-recalled echo SE = spin echo SI = signal intensity 2D = two-dimensional 3D = three-dimensional

Author contributions: Guarantor of integrity of entire study, J.F.D.; study concepts, J.F.D., W.L., J.M.F.; study design, W.L.; definition of intellectual content, J.F.D., W.L., J.M.F.; literature research, W.L., N.S., F.L., D.W.; experimental studies, W.L., N.S., F.L.; data acquisition, W.L., N.S., D.W.; data analysis, D.W.; statistical analysis, D.W., N.S.; manuscript preparation and editing, W.L., J.F.D., D.W.; manuscript review, J.F.D., D.W., J.M.F.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Luboldt W, Bauerfeind P, Steiner P, Fried M, Krestin GP, Debatin JF. Preliminary assessment of three-dimensional magnetic resonance imaging for various colonic disorders. Lancet 1997; 349:1288-1291.[Medline]
  2. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy: the National Polyp Study Workgroup. N Engl J Med 1993; 329:1977-1981.[Abstract/Free Full Text]
  3. Luboldt W, Steiner P, Bauerfeind P, Pelkonen P, Debatin JF. Detection of mass lesions with MR colonography: preliminary report. Radiology 1998; 207:59-65.[Abstract/Free Full Text]
  4. Hiraishi K, Narabayashi I, Fujita O, et al. Blueberry juice: preliminary evaluation as an oral contrast agent in gastrointestinal MR imaging. Radiology 1995; 194:119-123.[Abstract/Free Full Text]
  5. Layrisse M, Martinez Torres C, Divo MR, Jaffe W, Torres Suarez JE. Iron absorption from skim milk enriched with iron glycerophosphate (letter). Arch Latinoam Nutr 1973; 23:145-150.[Medline]
  6. Liebig T, Stoupis C, Ros PR, Ballinger JR, Briggs RW. A potentially artifact-free oral contrast agent for gastrointestinal MRI. Magn Reson Med 1993; 30:646-649.[Medline]
  7. Briggs RW, Wu Z, Mladinich CR, et al. In vivo animal tests of an artifact-free contrast agent for gastrointestinal MRI. Magn Reson Imaging 1997; 15:559-566.[Medline]
  8. Pobedinskaia VN. Use of large doses of iron glycerophosphate in the therapy and prevention of allergic diseases in children. Vopr Okhr Materin Det 1976; 21:61[Russian].
  9. Hallberg L, Solvell L, Brise H. Search for substances promoting the absorption of iron: studies on absorption and side-effects. Acta Med Scand Suppl 1966; 459:11-21.[Medline]
  10. Anghileri LJ, Cordova Martinez A, Maincent P, Robert J. In vivo behaviour of low molecular weight iron complexes. Eur J Drug Metab Pharmacokinet 1991; 16:203-206.[Medline]
  11. Lombard M, Chua E, O'Toole P. Regulation of intestinal non-haem iron absorption. Gut 1997; 40:435-439.[Free Full Text]
  12. Goei R, Nix M, Kessels AH, Ten Tusscher MP. Use of antispasmodic drugs in double contrast barium enema examination: glucagon or buscopan?. Clin Radiol 1995; 50:553-557.[Medline]
  13. Rubesin SE, Furth EE, Rose D, Levine MS, Laufer I. The effects of distention of the colon during air-contrast barium enema on colonic morphology: anatomic correlation. AJR 1995; 164:1387-1389.[Abstract/Free Full Text]
  14. Chouly C, Pouliquen D, Lucet I, Jeune JJ, Jallet P. Development of superparamagnetic nanoparticles for MRI: effect of particle size, charge and surface nature on biodistribution. J Microencapsul 1996; 13:245-255.[Medline]



This article has been cited by other articles:


Home page
 GutHome page
W Ajaj, G Pelster, U Treichel, F M Vogt, J F Debatin, S G Ruehm, and T C Lauenstein
Dark lumen magnetic resonance colonography: comparison with conventional colonoscopy for the detection of colorectal pathology
Gut, December 1, 2003; 52(12): 1738 - 1743.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
D. R. Martin, M. Yang, D. Thomasson, and C. Acheson
MR Colonography: Development of Optimized Method with ex Vivo and in Vivo Systems
Radiology, November 1, 2002; 225(2): 597 - 602.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
M. T. Keogan and R. R. Edelman
Technologic Advances in Abdominal MR Imaging
Radiology, August 1, 2001; 220(2): 310 - 320.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
C. D. Johnson and A. H. Dachman
CT Colonography: The Next Colon Screening Examination?
Radiology, August 1, 2000; 216(2): 331 - 341.
[Abstract] [Full Text]

Home page
 RadiologyHome page
W. Luboldt, P. Bauerfeind, S. Wildermuth, B. Marincek, M. Fried, and J. F. Debatin
Colonic Masses: Detection with MR Colonography
Radiology, August 1, 2000; 216(2): 383 - 388.
[Abstract] [Full Text]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Luboldt, W.
Right arrow Articles by Debatin, J. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luboldt, W.
Right arrow Articles by Debatin, J. F.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
RADIOLOGY RADIOGRAPHICS RSNA JOURNALS ONLINE