0 30 60 90 120 150 180 210 240

Time (mm)

Health and Medical Research Council ofAustralia and the RoyalAdelaide Hospital.

REFERENCES

I. Horowitz M, Collins PJ, Shearman DJC. Disorders of gastric emptyingand the use of radionuclide techniques. Arch Intern Med 1985:145:1467—1475.

2. Christian PE, Datz FL, Sorenson JA, Taylor A. Technical factors in gastricemptying studies. J NuciMed 1983;24:264—268.

3. Meyer JH, MacGregor IL, Gueller R, Martin P, Cavalieri R. TC-99m-tagged chicken liver as a marker of solid food in the human stomach. DigDisSci1976;21:296—304.

4. Malmud LS, Fisher RS, Knight LC, Rock E. Scintigraphic evaluation ofgastric emptying. Semin Nuc/Med l982;l2:1 16—125.

5. Carryer PW, Brown ML, Malagelada JR, Carison GL, McCall JT. Quantification of the fate of dietary fiber in humans by a newly developedradiolabeled fiber marker. Gastroenterology 1982;82:1389—l394.

6. Kerlin P, Byrnes 0, Wong L. Radiolabelled unprocessed bran: validationof a practical labelling technique and evaluation of gastrointestinal transitprofilesinhealth.J GastroHepazoll989;4:119—126.

7. Heading RC, Tothill P, Laidlaw AJ, Shearman DJC. An evaluation of1‘31n-DTPA chelate in the measurement of gastric emptying by scintiscan

fling.Gut l971;l2:6l1—615.8. Carey MC. Lipid digestion and absorption. Ann Rev Physiol l983;45:651—

677.9. Meyer JH, Mayer EA, Jehn D, Gu Y, Fink 5, Fried M. Gastric processing

and emptying of fat. Gastroenterology 1986;90:l 176—1187.10. Cortot A, Phillips SF, Malagelada JR. Gastric emptying of lipids after

ingestion ofa solid-liquid meal in humans. Gastroenterology 198l;80:922—927.

11. Cortot A, Phillips SF, Malagelada JR. Gastric emptying of lipids afteringestion ofan homogenized meal. Gastroenterology 1979;76:939—944.

12. Jian R, Vigneron N, Najean Y, Bernier JJ. Gastric emptying and intragastric distribution oflipids in man. Dig Dis Sci 1982;27:705—7l1.

13. Harper PV, Lathrop KA, Hinn GM, Cowan W, Schawer B. In: AndrewsCA, Kniseley RM, Wagner HN, eds. Radioactive pharmaceuticals. OakRidge, TN: USAEC Division of Technical Information Extension; 1965:353—356.

14. Harper PV, Lathrop KA, McCardle RJ. Improved liver scanning with 6hour 90mTcin fat emulsion [Abstract]. J NuciMed 1963:189.

15. Vogel Al. Calorimetric and stereophotometric analysis. In; Quantitativeinorganic analysis, third edition. London: Longmans, Green and Co., Ltd.;1961:786—787.

16. Collins PJ, Horowitz M, Cook DJ, Harding PE, Shearman DJC. Gastricemptying in normal subjects. A reproducible technique using a singlescintillation camera and computer system. Gut 1983;24:1 117—1125.

17. Goodman LS, Gilman A. Noxious gases and vapors. In: The pha@macologicalbasis oftherapeutics. fourth edition. New York: Macmillan; 1970:935.

18. Tinker TH, Michenfelder JD. Sodium nitroprusside: pharmacology, toxicology, and therapeutics. Anaesthesiology l976;45:34.

19. Merck Index, tenth edition. Rahway, NJ: Merck and Company Inc.;1983:9165.

100 Oil

Aqueous

C0

CG)

a)

FIGURE 4. Emptyingcurvesfor oilandaqueousphasesin avolunteer (same as for Fig. 3) who ingested 290 ml of beefconsommesoup(labeledwithll3mlnDTpA)blendedwith60gofoliveoillabeledwith @mTc(V)thiocyanate.

ble as lipid labels because the pertechnetate formed willrapidly return to the aqueous phase.

Radionuclide methods have confirmed that there aresignificant differences in the rates at which different foodcomponents (digestible solids, nondigestible solids, liquids,and fats) empty from the stomach in humans (1—7,12,16). Technetium-99m is the preferred radionuclide forimaging purposes because of its low cost, low radiationburden, and favorable gamma ray energy. We believe that99mTc(V)thiocyaflate is a valuable addition to the range ofpharmaceuticals that may be used to study gastric emptying.

ACKNOWLEDGMENTS

The authors wish to thank Mrs. M. Marucci for typing thismanuscript. This work was supported by grants from the National

I n this issue, Cunningham et al. de- is one of several important considerscribe a radiopharmaceutical for ations in accurately measuring the

measuring the gastric emptying of fat rate of gastric emptying.(1). The choice ofradioactive markers

non-nutrient saline meals empty rapidly with exponential (first-order) kinetics, whereas nutrient meals showan initial emptying period that loadsthe duodenum, followed by a morelinear (zero-order) emptying curve(2).

Second, solid-phase markers shouldbe used. The mechanism of liquid

Received Jan. 9, 1991 ; accepted Jan. 9, 1991.For reprints contact: Frederick L. Datz, MD,

Division of Nuclear Medicine, University of UtahMedical center, 50 North MediCal Dr., Salt Lakecity,UT84132.

ConsiderationsforAccuratelyMeasuringGastricEmptyingofFat•Datz 881

EDITORIAL

Considerationsfor AccuratelyMeasuringGastricEmptying

RADIOPHARMACEUTICAL

First, it is important that food beused as the marker of gastric emptying. Hunt and Stubbs have shown

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99mTc and ‘‘‘In-labeledchicken liverhave markedly different dosimetries.Compared to 99mTc 500 @Ciof “Inlabeled chicken liver results in a stomach dose 4 times higher, a large intestine dose 20 times higher, and a totalbody burden 12 times greater (15).

TECHNIQUE

Patient positioning must be standardized. A study of the rate of gastricemptying in subjects in four differentpositions (recumbent, sitting, standing, and alternate sitting-standing) indicated the recumbent positionslowed gastric emptying by 102%compared to sitting-standing (16).How recumbency slows gastric emptying is unknown, but likely it is related to meal pooling, reduced antraldistention, and lack of a gravitationaleffect. Because exercise, even walking,enhances gastric emptying, it is important that subjects remain quiescentbetween imaging sessions (1 7).

The interval between imaging canalso affect accuracy. Obviously, thefewer the data points, the more likelythe true half-emptying time will bemissed; the controversy about thepresence or absence ofan initial solidphase lag period is partly related tothis problem (18). Studies with continuous monitoring show a short mitial lag phase (8 mm), which could bemissedeasilyif samplingisdoneonlyat 10—15-mm intervals, as is frequently the case. Continuous monitoring has another advantage: it prevents the patient from falsely enhancing gastric emptying by walkingbetween imaging sets.

Patient motion during acquisitionor inaccurate repositioning will causeerrors, usually falsely shortened emptying times (19). This is because stomach activity will move outside the outline of the stomach region of interest,falsely lowering the counts measured.

Repositioning is frequently done bymarking the stomach region with awax pencil on the persistence scope.The patient is positioned with thestomach activity within this area atthe beginning ofeach imaging session.A better method is to tape a small

emptying is different from solid emptying and liquids may give normalemptying times in the presence of disease (3). Liquid emptying is primarilydependent on the effects of gravityand the pressure gradient between thestomach and duodenum.

The control of post-prandial solidemptying is much more complex.Studies in dogs indicate solid foodmust be reduced to a maximum sizeof 1 mm before it can enter the duodenum, with the majority of particlespassed measuring 0.06 mm or less (4).Surprisingly, the fragmentation offood is primarily dependent on thecoordinated contraction of the stomach walls. In fact, although enzymaticdigestion may contribute to fragmentation, it is not necessary and normalemptying rates can occur in its absence (6). This grinding activity is dependent on the antrum rather thanthe fundus and is controlled by thepost-prandial propagation of peristaltic waves (3). Solids can also emptythe stomach via powerful Phase IIIinterdigestive migrating motor complex (MMC) contractions that occurbetween meals. These powerful lumen-obliterating contractions arestimulated by motilin. Their purposeis to empty the stomach of indigestibledebris and fasting contents. Erythromycin, shown recently to enhancegastric emptying in diabetic gastroparesis, does so by binding to motilinreceptors (7).

Meal caloric content must also beconsidered. Using liquid-meal emptying times determined by a tube-indicator recovery technique, Hunt andStubbs showed gastric emptying wasslowed with increasing caloric density(kcal/g) (8). Equicaloric concentrations of lipid, carbohydrate, and protein produced equal slowing of gastricemptying rates. This concept is sometimes referred to as the Hunt andStubbs hypothesis and states that gastric emptying is controlled by the nutrientdensity(totalkcal/totalg or mlof food) entering the duodenum (9).Studies using radionuclide techniqueswith solids have been consistent withthis hypothesis (10,11). A 300-g meal

with a total caloric content of 68 kcalemptied with a half-time of 73 mm,while a similar-sized meal containing633 kcal emptied with a half-time of214 mm (11).

Studies have indicated that an evenmore important criterion is meal sizeor weight (10,11). As meal size increases, gastric emptying slows. Mealsof 300, 900, and 1692 g caused solidemptying times of 77 mm, 146 mm,and 277 mm, respectively; liquidsshowed half-emptying times of 40mm, 81 mm, and 178 mm, respectively (10). When caloric content andmeal weight are compared, the slowing effect of added calories is not sufficient to overcome the enhancing effect of increasing meal weight. In astudy using meals of equicaloric content, a 300% increase in meal weightresulted in a 388% increase in absolute emptying rates, while a 304% increase in total meal calories causedonly a 43% reduction in absoluteemptying rates (11).

Stability of the solid-phase tag isalso important. If the tag elutes, itmixes with the liquid phase, giving apartly solid, partly liquid, emptyingtime. To prevent problems from tagelution, Meyers et al., developed an invivo technique for labeling chickenliver (12). Stability is excellent: 97%—98% of the tag is still associated withthe liver after 4 hr of incubation ingastric juice or hydrochloric acid. Unfortunately, the technique is inconvenient, requiring the injection andsacrifice of live chickens. Until recently, alternative techniques havegiven much higher dissociation percentages (13,14).

A simple labeling technique of liverthatdoesnotrequirelivechickenshasrecently been developed (14). Thistechnique involves frying liver pate ina mixture of 99mTcsulfur colloid. Incubation studies indicate 92%—93%ofthe tag remains bound at 4 hr. This ismore than adequate for gastric emptying studies.

Finally, the radioisotope chosen formarking the food must be considered.Higher-energy isotopes are attenuatedless;however,equivalentactivitiesof

882 The Journal of Nuclear Medicine •Vol. 32 •No. 5 •May 1991

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point-source marker of 57Co or 99mTcon the patient's skin (3). The locationof the marker is drawn on the persistence scope at the first imaging session.Then the patient is positioned withthe marker in the drawn region eachtime. If both anterior and posteriorimaging are performed, a secondmarker should be placed on the patient's back. Not only do the markerspermit accurate vertical and horizontal repositioning, they allow any patient motion during image acquisitionto be discovered. Motion artifacts canbe corrected by drawing a new regionof interest for each image set.

Depending on the radionuclidesused, decay correction may be necessary. Isotopes with short half-lives,such as 99mTcor ‘‘3mIfl must be decaycorrected or the emptying time will beunderestimated (20). This is especially important for patients with significantly delayed emptying. Indium111, on the other hand, with its 2.7-day half-life, does not require correction.

In simultaneous solid-liquid phasestudies using 99mTc and ‘‘‘Inas themarkers, a correction for crosstalkmust also be made (20). Using moreactivity of the lower energy isotopethan the higher-energy radionuclidehelps minimize the effects of downscatter. In addition, estimates can bemade of the amount of down-scatterinto the lower energy window; thesecounts can then be subtracted fromthe measured counts in the lower-energy window. Since correction factorsdepend on the relative amounts ofactivity used for each radionuclide,the window width, and the recordedpercentage of scatter into the lowerwindow, it is best to experimentallydetermine the degree ofcrosstalk fromphantom or patient studies and usethis number for correction.

Gastric emptying studies are a dynamic process in which the radiolabeled food progresses from an initialposterior position in the fundus to themore anteriorly-located antrum. Ifimaging is performed from the anterior position only, an artifactitious increase in counts occurs as the radio

nuclide's depth within the body decreases and attenuation plus scatterare reduced (3,20).

How important are these effects?Studies indicate gastric emptying ratesare underestimated (half-times overestimated) by an average of38% usinga standard 300-g meal (21). Errors aslarge as 87%, however, are seen inindividual patients. The effect varieswith meal size (20,21).

There are several approaches forcorrecting for depth and attenuation.We use opposed detectors and geometric mean correction. At each imaging session, anterior and posteriorcountsin the stomachare recorded.The geometric mean is calculated by:(anterior counts X posterior counts)l/2. Phantom studies indicate the calculated geometric mean gives countrates that vary less than 2% for depthsof2.5—20 cm (21).

An alternative approach for correction of depth and scatter (as well asseptal penetration) is to use the peakto-scatter(P/S) ratio(20,22,23).Studies of ‘l3mIflwith its 392-keY photon,indicate attenuation is less importantthan scatter and septal penetration,when compared to 99mTc Errors of30%—40% have been found withI 3mIfl Studies indicate a correction

factor generated from the P/S ratiomay give equivalent results to geometric mean correction (22,23). Investigations into the use of the P/Sratio in linear profile scanning, however, indicate the P/S ratio methodmay be more sensitive than the geometric mean technique to variationsin source volume and other distribution effects (24). In particular, the P/S ratio can be changed by scatter fromsources completely outside the fieldof view of the camera. Therefore, it isnot clear that the P/S ratio methodoffers any advantage compared to thesimpler geometric mean correctiontechnique.

PHYSIOLOGICVARIABLES

In establishing and applying normal emptying values, several pointsmust be considered. First is the timeofday of the study. Circadian rhythm

affects gastric emptying as it doesother physiologic processes (25). In astudy of healthy subjects who underwent identical gastric emptying studies at 8 a.m. and at 8 p.m., eveningemptying rates were significantlyslower than morning rates. Therefore,it is important that gastric emptyingstudies always be scheduled at thesame time each day to ensure thatestablished normal values apply.

Even more important is to establishdifferent normal values for males andpre-menopausal females. In the past,it wasassumedmenandwomenhadidentical rates of gastric emptying.Normal values were usually established in male volunteers and thenapplied to both sexes; however, studies of normal pre-menopausal womenhave shown they have significantlyslower gastric emptying than men.Since post-menopausal women havemuch more rapid emptying, equal tothat of men, female sex hormonesappear to inhibit gastrointestinal motility (27).

Estradiol and progesterone mayslow gastric emptying by two mechanisms. Estradiol receptors have beenidentified in gastrointestinal tissuesand progesterone receptors are likelypresent as well (26). Female sex hormones may, therefore, directly affectmotility. Second, motilin, a gastrointestinal hormone with smooth muscle-stimulating effect is decreased inpregnancy. Progesterone may act indirectly in slowing gastric emptyingby decreasing plasma levels of motilin(26).

Finally, subjects need to be at easeduring the gastric emptying exam.Physical stress slows gastric emptying,and mental stress may do the same(28).

Gastric emptying studies are a useful tool for investigating normal physiology and detecting gastrointestinaldisease. Strict attention to detail whencarrying out the studies is necessary,however, to ensure accurate results.

Frederick L. DatzUniversity of Utah School of

MedicineSalt Lake City, Utah

883ConsiderationsforAccuratelyMeasuringGastricEmptying•Datz

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20. Christian PE, Datz FL, Sorenson JA, et al.Technical factors in gastric emptying studies. JNuclMed 1983;24:264—268.

21. Christian PE, Moore JG, Sorenson JA, et al.Effects of meal size and correction techniqueon gastric emptying time: studies with twotracers and opposed detectors. J Nucl Med18021:883—885.

22. VanDeventer G, Thomson J, Graham LS, etal. Validation of corrections for errors in collimation on measuring gastric emptying of nuclide-labeled meals. J NucI Med 1982:24:187—196.

23. Meyer JH, VanDeventer G, Graham IS, et al.Error and corrections with scintigraphic messurement of gastric emptying of solid foods. JNuclMed l982;24:197—203.

24. Sorenson JA. Methods for quantitating radioactivity in vivo by external counting measurements. PhD Thesis. University Wisconsin,1971.

25. Goo RH, Moore JG, Greenberg E, et al. Cirradian variation in gastric emptying of mealsin humans. Gastroenterology 1987;93:515—518.

26. Data FL, Christian PE, Moore JG. Genderrelated differences in gastric emptying. J NuclMed l987;28:1204—1207.

27. Data FL, Christian PE, Moore JG. Differencesin gastric emptying rates between menstruatingand post-menopausal women [Abstract]. JNuclMed l987;28:604—605.

28. Datz FL, Christian PE, Hutson WR, et al. Theeffect of physical and psychologic stress ongastric emptying. J Nucl Med 1990;31:800—801.

sition in man—evaluation by dual-liquid andsolid-phase isotopic method. Dig Dis Sci198l;26: 16—22.

11. Moore JG, Christian PE, Brown JA, et al.Influence of meal weight and caloric contenton gastric emptying of meals in man. Dig DisSci l984;29:5 13—519.

12. Meyer JH, MacGregor IL, Guellar R, et al. Tc99m-tagged chicken liver as a marker of solidfood in the human stomach. Am J Dig Dis1976;21:296—304.

13. Knight LC, Malmud LS. Tc-99m-ovalbuminlabeled eggs: comparison with other solid foodmarkers in vitro [Abstract]. J NucI Med1981,22:P28.

14. Christian PE, Moore JG, Datz FL. ComparisonofTc-99m-labeled liver and liver pate as markera forsolid-phasegastricemptying. JNuclMedl984;25:364—366.

15. SiegelJA, Wu RK, Knight LC, et a!. Radiationdose estimates for oral agents used in uppergastrointestinal disease. J Nucl Med1983;24:835—837.

16. Moore JG, Datz FL, Christian PE, et al. Effectofbody posture on radionuclide measurementsofgastricemptying.DigDisScil988;33:1592—1595.

17. Moore JG, Datz FL, Christian PE. Exerciseincreases solid meal gastric emptying rates inmen. Dig Dis Sci 1990;35:428—432.

18. Datz FL, Christian PE, Moore JG. Confirmation of short solid food lag phase with continuous monitoring of gastric emptying. J NuclMed l987;28:563.

19. Glowniak JV, Wahl RL. Patient motion artifacts on scintigraphic gastric emptying studies.Radiology1985;l54:537—538.

884 The Journal of Nuclear Medicine •Vol. 32 •No. 5 •May 1991

REFERENCES

1. Cunningham KM, Baker RJ, Horowitz M, etal. Use of Tc-@m-(V)thiocyanate to measuregastric emptying of fat. I Nucl Med 1991;32:878—881.

2. Hunt JW, 5tubbs DF. The volume and energycontent of meals as determinants of gastricemptying. J Physiol 1979;245:209—225.

3. Christian PE, Datz FL, Moore JG. Technicalconsiderations in radionuclide gastric emptyingstudies. JNuclMed Technol 1987;l5:200—207.

4. Meyer JH, Thomson JB, Cohen MB, et al.Sieving a solid food by the normal and uleeroperated canine stomach. Gastroenterology1979;76:804—813.

5. Ohashi H, Meyer JH. Effect ofpeptic digestionon emptying of cooked liver in dogs. Gastroenterology1980;79:305—310.

6. MeyeriH, Ohashi H, Jehn D, et al. Size of liverparticles emptied from the human stomach.Gastroenterology 1980;80:1489—1496.

7. Janssens J, Peeters TL, Vantrappen G, et al.Improvement of gastric emptying in diabeticgastroparesis by erythromcyin—preliminarystudies.N EnglJMed 1990;322:1028—1031.

8. Heading RC, Tothill P. McLoughlin GP, et al.Gastric emptying role measurement in mana double-isotope scanning technique for simultaneous study of liquid and solid componentsofa meal. Gastroenterology 1976;71:45—50.

9. Hunt JW, Stubbs DF. The volume and energycontent of meals as determinants of gastricemptying. J Physiol 1975;245:209—225.

10. Moore JG, Christian PE, Coleman RE. Gastricemptying of varying meal weight and compo

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1991;32:881-884.J Nucl Med.   Frederick L. Datz  Considerations for Accurately Measuring Gastric Emptying

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