252

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ing. Radiology i989;172:739-743 Reiser M, Bohndorf K, Niendorf HP, Friedmann G, Erlemann A, Kunze V. Preliminary results with gadolinium-DTPA in magnetic resonance tomography of bone and soft-tissue tumors. Radio!oge i987;27:467-472 51 . Pettersson H, Eliasson J, Egund N, et al. Gadolinium-DTPA enhancement of soft tissue tumors in magnetic resonance imaging: preliminary clinical experience in five patients. Skeletal Radio! i988;17:3i9-323 52. Erlemann A, Aeiser MF, Peters PE, et al. Musculoskeletal neoplasms: static and dynamic gadopentetate enhanced MR imaging. Radiology 1989:171:767-773 53. Kim E, Abello A, Holbert JM, et al. Differentiation of therapeutic changes

AJR:i56,

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50.

Gastrointestinal Peter

Contrast

55.

56.

1991

from recurrent or residual musculoskeletal sarcomas with gadopentetate enhanced MA imaging. Radiology i989;173(P): 104 Bottomley PA, Hardy RE, Argersinger RE, Allen-Moore G. A review of iH nuclear magnetic resonance relaxation in pathology: are Ti and T2 diagnostic? Med Phys i987;i4: 1-37 Weissleder A, Elizondo G, Josephson L, et al. Experimental lymph node metastases: enhanced detection with MR lymphography. Radiology i989;171 :835-839 Hamm B, Taupitz M, Wagner 5, Hussmann P. Wolf KJ. MR lymphography: initial experimental results with superparamagnetic iron oxide. Radiology i989;i 73(P):274

Agents

F. Hahn

There is widespread agreement that development of a gastrointestinal contrast agent will be necessary for abdominab MR imaging to progress. For example, one reason that MR imaging of the liver has not been adopted more widely, despite evidence that it can compete favorably with CT in detecting and characterizing focal hepatic lesions, is that examinations performed to stage cancer in the liver routinely miss three times as many important extrahepatic lesions as CT does [i 2]. Although issues of noise and spatial resolution must be confronted, bowel marking, with confident delineation of the pancreas and paraaortic area, seems an essential prerequisite for expanding the use of MR beyond the liver. In general, MR contrast agents for use in the gastrointestinal tract may be classified according to whether they contribute signal to the bowel lumen (positive contrast agent) or reduce signal normally associated with the bowel lumen (negative contrast agent). This classification must be used cautiousby, however, because changes in concentration, technical factors, and physiologic conditions can change a positive contrast agent into a negative agent. For example, although gadolinium compounds usually increase signal intensity by shortening Ti higher concentrations of these compounds and more heavily T2-weighted imaging can result in predominance of the T2-shortening effect, resulting in a decrease in signal intensity. Thus, an agent that began in the stomach as a positive agent might, after concentration in the colon by physiologic water resorption, become a negative agent. A second useful distinction can be made between contrast agents intended to mix with bowel contents, so-cabled miscible agents, and those intended to replace bowel contents, immiscible agents. Table i displays many of the materials that have been tested as gastrointestinal contrast agents, separated according to the positive-negative and miscibleimmiscible characteristics. ,

,

Positive

54.

February

Agents

Positive contrast netic substances,

agents for MR imaging include which mix with bowel contents,

paramagand fats

and oils, which must replace bowel contents in order to mark the bowel. Although fatty materials, with inherently short Ti, were among the earliest materials investigated for oral contrast in MR imaging [3], delivery of sufficient volume to replace all of the small-bowel contents has not been reported. Gadopentetate dimeglumine has been developed for use as an oral contrast agent (Fig. i). With conventional spin-echo and gradient-echo techniques and doses on the order of 500-700 ml of 1 mmol/l solution, gadopentetate dimeglumine is a positive contrast agent that mixes with gastrointestinal tract contents, shortening Ti [4]. In order to ensure delivery deep into the small bowel, gadopentetate dimeglumine is given with a nonabsorbable sugar such as i 5-30 g of mannitol. Positive contrast agents can increase image noise through motion of the bowel during imaging. Therefore, investigators using oral gadopentetate dimeglumine have obtained best results with fast gradient-echo imaging, abdominal compression, and pharmacologic reduction of bowel peristabsis. Other paramagnetic substances have been investigated as oral contrast agents. The first proposed for this purpose was ferric ammonium citrate [5], widely available as the hematinic in Geritol (Beecham, Bristol, TN). Ferric ammonium citrate produces about one fifth as much Ti shortening as gadopentetate dimeglumine does at equal concentrations. At first only limited delivery offerric ammoniurn citrate into the small bowel was achieved. Recently, a mixture of ice cream (30%), corn oil (20%), milk (38%), and ferric ammonium citrate (1 2%) has been found to be well tolerated and to achieve positive gastroduodenal and small-bowel marking [6]. Negative

Agents

Negative contrast agents include clays, barium sulfate, iron oxides, perfluorocarbons, and gas-evolving pellets. The clay mineral kaolin used to be in the nonprescription medication Kaopectate (Upjohn, Kalamazoo, Ml). Kaolin is on the U.S. Food and Drug Administration list of substances generally recognized as safe for use as an indirect food additive. Kaolin produces diamagnetic Ti and T2 shortening in aqueous sus-

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AJA:156,

February

ADVANCES

1991

IN CONTRAST-ENHANCED

pension, the T2 effect predominating. Consequently, kaolin is a negative contrast agent, and oral administration of 950 ml Kaopectate has been shown to produce gastric and duodenal marking in humans [7]. Although kaolin is readily available, other clays may ultimately prove to be more effective for bowel contrast. Barium sulfate is another familiar and widely available material that can be used to produce a negative contrast effect. Concentrated banums (60-70%) have been advocated as more effective oral gastrointestinal MR contrast agents [8]. Early experience with patients imaged after oral administration of barium indicates that this contrast agent marks the stomach and duodenum on MR images and can be useful for delineating the pancreas until a more favorable MR contrast agent becomes available [9]. TABLE Agents

1: Classification for MR Imaging

of Gastrointestinal

Miscible Positive agents Negative

agents

Gadopentetate Ferric ammonium Barium sulfate Clays Superparamagnetic

Tract

Agents

Contrast

Immiscible

dimeglumine citrate

Agents

Fats and oils Perfluorocarbons Gas

iron

oxides

Fig. i.-Gadopentetate dimeglumine administered as oral contrast agent. SE 500/15 (i.5 T) MR images. A, Before contrast ingestion, stomach (5) is poorly distended; head of pancreas (arrow) is isointense with duodenum (D). B, After contrast ingestion, stomach and duodenum are distended and opacified by highsignal-intensity contrast material, producing good delineation of pancreatic head.

Fig. 2.-Superparamagnetic iron oxide administered as oral contrast agent. SE 2350/60 (i.5 T) MR images. A, Precontrast image shows pancreas (P) adjacent to nearly isointense duodenum (D) and small bowel (B). B, Postcontrast image shows signal void in stomach (5), duodenum, and small bowel crcated by iron oxide. Sp = spleen, C = gallbladder.

MR

IMAGING

253

Development of superparamagnetic iron oxide particles as gastrointestinal contrast agents followed their application in IV administration. Initial studies showed insufficient dynamic range, limited by artifacts produced by distortion of the magnetic field where particles concentrate in excess [1 0]. New preparations of iron oxide particles have been subjected to clinical trial as oral contrast agents (Fig. 2) [i 1 i2]. Careful particle design with particle size and other factors controlled to ensure prolonged homogeneous suspension is necessary to produce an agent that does not cause distortion [i 0]. Bowel loops containing iron oxide can be uniformly darkened with iOO mg of iron. T2-weighted images are more sensitive to the contrast agent than are Ti -weighted images. Perfluorocarbons also produce negative gastrointestinal tract contrast. Unlike the particulates, which are intended to mix with bowel contents, perfbuorocarbons are immiscible. They act by replacing bowel contents with a material backing protons and that therefore produces no proton MR signal. Perfluorooctylbromide (PFOB) has been studied in humans, producing readily identified loss of signal in the small bowel [i 3, i4]. PFOB transit time is rapid, so that the stomach may be nearly empty of contrast agent within 5 mm of ingestion. Gas in the bowel produces a signal void that can be exploited to distend the gut and to produce contrast between bowel ,

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254

HAHN

lumen and surrounding organs. Bowel gas can be associated with distortion of the signal from structures adjacent to the bowel through a magnetic susceptibility effect. Gas also may be introduced by oral ingestion of effervescent granules [15]. Pharmacologic paralysis of the bowel has been helpful in maintaining distension during imaging. This method has been advocated for outlining the pancreas [1 6, i 7]. Air instilled through a rectal tube has proved useful in defining rectal carcinomas so that depth of invasion can be ascertained [i8]. Several pediatric food formulas affect the signal in bowel. Although none has been developed systematically as a bowel contrast agent, administration of these materials before imaging has sometimes been found useful for imaging young children [i9]. At present, no one MR contrast agent has been shown to be superior for gastrointestinal applications. Valid comparison studies will be extremely difficult to perform, particularly while the MR imaging parameters continue to change. As the protocols become better defined, indications for specific types of contrast material may emerge.

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1 . Ghezmar JL, Rumancik WM, Megibow AJ, Hulnick DH, Nelson AG, Bernardino ME. Liver and abdominal screening in patients with cancer. CT versus MR imaging. Radiology i988;i 68:43-47 2. Stark DD, Wittenberg J, Butch AJ, Ferrucci JT Jr. Hepatic metastases: randomized, controlled comparison of detection with MA imaging and CT. Radiology i987;165:399-406 3. Newhouse JH, Pykett IL, Brady TJ, et al. NMR scanning of the abdomen: preliminary results in small animals. In: Witcofski AL, Karstaedt N, Partain CL, eds. Proceedings of the Symposium on Nuclear Magnetic Resonance Imaging. Winston-Salem, NC: Bowman Gray School of Medicine, Wake Forest University, i98i;121 -124 4. Laniado M, Kommesser W, Hamm B, Clauss W, Weinmann H-J, Felix A. MA imaging of the gastrointestinal tract: value of Gd-DTPA. AJR

1991

i988;i 50:817-821 5. Wesbey GE, Brasch AC, Engelstad BL, Moss AA, Crooks LE, Brito AG. Nuclear magnetic resonance contrast enhancement study of the gastroin-

6. 7. 8.

9. 1 0.

11.

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13.

14. REFERENCES

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16.

17.

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testinal tract of rats and a human volunteer using nontoxic oral iron solutions. Radiology 1983:1 49: 1 75-i 80 Ang PGP, Li KGP, Tart AP, Storm B, Rolfes A. Geritol oil emulsion: ideal positive oral contrast agent for MR imaging. Radiology i989;172(P):522 Listinsky JJ, Bryant AG. Gastrointestinal contrast agents: a diamagnetic approach. Magn Reson Med i988;8:285-292 Tart AP, Li CPK, Fitzsimmons JA, Storm B, Mao J. Barium sulfate suspension as a negative oral contrast agent in MA imaging. Radiology 1989:1 72(P):52i Burton SS, Ros PA, Otto PM, et al. Barium MA imaging of the pancreas: initial experience. Radiology i989;i 72(P): 517 Hahn PF, Stark DD, Saini 5, Lewis J, Wittenberg J, Ferrucci JT. Ferrite particles for bowel contrast in MR imaging: design issues and feasibility studies. Radiology 1987:164:37-41 LOnnemark M, Hemmingsson A, Bach-Gansmo T, et al. Effect of superparamagnetic particles as oral contrast medium at magnetic resonance imaging. Acta Radio! i989;30: 193-i 96 Hahn PF, Stark DD, Saini 55, et al. Clinical evaluation of superparamagnetic iron oxide particles as a gastrointestinal contrast agent for MR imaging. Radiology i989;i 72(P): 160 Mattrey AF, Hajek PC, Gylys-Morin VM, et al. Pertluorochemicals as gastrointestinal contrast agents for MA imaging: preliminary studies in rats and humans. AJR i987;i 48:1259-1263 Mattrey AF. Perfluorooctylbromide: a new contrast agent for CT, sonography, and MR imaging. AJR i989;i 52:247-252 Zerhouni EA, Brennecke CM, Fishman EK, Zimmer A, Soulen AL. Development of a gaseous contrast agent for MRI of the abdomen and pelvis. Proceedings of the 34th annual meeting of the Association of University Radiologists. Hartford, CT, i986;abstract no. 63 Jenkins JPR, Braganza JM, Hickey DS, Isherwood I, Machin M. Quantitative tissue characterisation in pancreatic disease using magnetic resonance imaging. Br J Radiol 1987:60:333-341 Weinreb JC, Maravilla KR, Aedman HG, Nunnally A. Improved MR imaging of the upper abdomen with glucagon and gas. J Comput Assist Tomogr i984;8:835-838 Butch AJ, Stark DD, Wittenberg J, et al. Staging rectal cancer by MA and

GT.AJR i986;i46:1i55-i160 19. Gerscovich EO, McGahan JP, Buonocore MH, Ablin DS, Lindfors rediscovery of infant feeding formula with magnetic resonance Pediatr Radiol i990;20:i47-i5i

KK. The imaging.

Advances in contrast-enhanced MR imaging. Gastrointestinal contrast agents.

252 HAHN ing. Radiology i989;172:739-743 Reiser M, Bohndorf K, Niendorf HP, Friedmann G, Erlemann A, Kunze V. Preliminary results with gadolinium-DT...
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