9
solid gastric emptying simultaneously (4). However, the technique of multiple radionuclide markers and labeling requires a well-equipped laboratory, and the examination procedure imposes a substantial amount of radiation on the patient (5). To minimize the radiationhazardfor the patient and to make measurementof gastric emptying more acces sible to standard hospital practice, the authors set out to develop breath tests for measuring gastric emptying of solids and liquids. The radiopharmaceutical‘4C-octanoic acid was selected as a marker for the solid phase. The results ofthese studies have been published recently (6). In addition, ‘3C-glycine was selected as a markerof the liquid phase because it is easily solubilized in water and rapidly absorbed and converted into ‘3C02 after it enters the small intestine. A ‘3C liquid marker was used, not only to elm inate radiationhazard, but also to allow simultaneous mea surement of both the solid and liquid phase of the meal. The ‘4C-octanoicacid and the 13C-glycine breath test were evaluated by performing simultaneous radioscintigraphic and breath-test measurements of a quadruple-labeledtest meal in 27 subjects. METhODS Sub@ts Ten healthyvolunteers (threewomen and seven men, mean age 25 yr. range 19—27 yr) and 17 patients (10 women and seven men, meanage43 yr, range19—65 yr)withdyspepticsymptomswere included in the study. The subjects had no history of previous gastrointestinalsurgery and were not taking any medicationa! fectinggastricmotility.Thegastricemptyingrateofthe liquidand solid phase of the test meal was measured simultaneouslyby radioscintigraphy and by ‘3C02/'4C02breath sample analysis. Test Meal All subjects performed the test at 8:00 a.m. after an overnight fast of at least 12 hr. The test meal consisted of a beaten egg, two slices ofwhite breadand5 g ofmargarine. The eggwas dosed with 74 kBq of [1-'4C]-octanoic acid, sodium salt (DuPont, NEN Re search,Boston,MA)and110MBqof @â€oeTc-albumin colloid(UI tra Technicow, MalinckrodtMedical, Petten, The Netherlands). Afterhomogenization, the yolkwas bakedseparatelyfromthe egg whitetoensurefirmlabeling. Theeggwhitewasbakedaroundthe yolkafterward. Themealwasingestedwithin10mis,immediately followedby 150mlofwater, dosedwith 100mgof [1-'3CJ-glycine The aim of the presentstudywas to developa duat-carbon labeledbreathtestforsimultaneously measuringgastricempty ingratesofliquidsandsolidswithsignificantiy lessradiation burdento the patientthan the radioSdrthgraphic technique. Methods: A test meal was used in which the liquid phase was labeledwithtwomarkers, i.e.,3.7 MBqof 1111n-DTPA and 100 mg of 13@g@ns@ thesolidphasealsowasduallylabeledwith 110 MBq of @c-atbur@n col@dand 74 kBq of @ acid.Simultaneous radiosdnbgraphic andbreath-test measure mentswere performedin 27 subjects,10 normalcontrolsand 17 @ents withdyspepticsymptoms.Mathematicanatysisofthe excretion rate of labeled CO2 allowed the definition of four pa rameters, i.e.,thegasthcempt@ngcoefficlant, the gastrichaff emptyingtime,thepeakexcretion timeandthe lag phase.Re suits: Therewasa goodto excellentcorrelationbetweenthe gastricemptyingcoefficient andthescintigraphichalf-emptying time (r = 0.74 for liquids and r = 0.88 for solids), between the half-emptying time determinedby breathtest and the scinti graphichalf-emptying lime (r = 0.91forliquidsandr = 0.92for solids),betweenthe peakexcretiontimearidthesdntigraphic half-emptying time(r = 0.91for liquidsandr = 0.96for solids) andbetween thelagphaseOtsolidemptyingdeterminedbyboth techniques (r = 0.89). ConclusIon: The duat carbon-labeled breathtest is a valid,minimally invasivetechniqueto measure the gastric emptying rate of both liquids and solids. Key Words: gastric emptying; breath test; radiosdrthgraphy; carbon-14-octanoic acid;carbon-13-glycine; indium-iI 1-DTPA; technetium-99m-albumin J Nuci Med 1994; 35:824-831 he solid, liquid and oil phase of a meal are handled differently by the stomach and are emptied at different rates. Accurate measurementofgastric emptying in normal and pathologic conditions requires that these be measured separately (1—3).Radioscintigraphic techniques with two different radionucides allow the measurement ofliquid and Received Jul 8,1993; revision accepted Jan.26,1994. Forcorrespondence orreprints cor*@Prct.Dr.P.Rutgeerts, Depaitment of Medicine andMedical Research, University Hospital Gasthulsbei@, B-3000 Leu van,B@m. 824 The Joumatof NuclearMedicine• Vol. 35 • No. 5 • May 1994 Combined Carbon-13-Glycine/Carbon- 14- Octanoic Acid Breath Test to Monitor Gastric Emptying Rates of Liquids and Solids B.D. Maes, Y.F. Ghoos,B.J. Geypens,0. Mys, M.I. Hide, P.J. Rutgeertsand 0. Vantrappen Depart@nent ofMedicüze@ Division of Gastroenterolgy and Gastrointestinal Research Centtr, University Hospital GasthuLtheig; and Department ofMathematics, Leuven@Belgium by on July 30, 2020. For personal use only. jnm.snmjournals.org Downloaded from

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solid gastric emptying simultaneously (4). However, thetechnique of multiple radionuclide markers and labelingrequires a well-equipped laboratory, and the examinationprocedure imposes a substantial amount of radiation on thepatient(5). To minimizethe radiationhazardfor the patientand to make measurementof gastric emptyingmore accessible to standard hospital practice, the authors set out todevelop breath tests for measuring gastric emptying ofsolids and liquids. The radiopharmaceutical‘4C-octanoicacid was selected as a marker for the solid phase. Theresults ofthese studies have been published recently (6). Inaddition, ‘3C-glycinewas selected as a markerof the liquidphase because it is easily solubilized in water and rapidlyabsorbedand converted into ‘3C02after it enters the smallintestine. A ‘3Cliquid marker was used, not only to elminate radiationhazard,but also to allow simultaneousmeasurement of both the solid and liquid phase of the meal.The ‘4C-octanoicacid and the 13C-glycine breath test wereevaluated by performing simultaneous radioscintigraphicand breath-test measurements of a quadruple-labeledtestmeal in 27 subjects.

METhODS

Sub@tsTen healthyvolunteers (threewomen andseven men, meanage

25 yr. range 19—27yr) and 17patients (10women and seven men,meanage43yr, range19—65yr)withdyspepticsymptomswereincludedin the study. The subjects had no history of previousgastrointestinalsurgery and were not taking any medicationa!fectinggastricmotility.Thegastricemptyingrate ofthe liquidandsolid phase of the test meal was measured simultaneouslybyradioscintigraphy and by ‘3C02/'4C02breath sample analysis.

Test MealAll subjects performed the test at 8:00 a.m. after an overnight

fast of at least 12 hr. The test meal consisted of a beaten egg, twoslices ofwhite breadand5 g ofmargarine.The eggwas dosed with74 kBq of [1-'4C]-octanoic acid, sodium salt (DuPont, NEN Research,Boston,MA)and110MBqof @“Tc-albumincolloid(UItra Technicow, MalinckrodtMedical, Petten, The Netherlands).Afterhomogenization,theyolkwas bakedseparatelyfromtheeggwhitetoensurefirmlabeling.Theeggwhitewasbakedaroundtheyolkafterward.Themealwasingestedwithin10mis, immediatelyfollowedby 150mlofwater, dosedwith 100mgof [1-'3CJ-glycine

The aim of the presentstudywas to developa duat-carbonlabeledbreathtestforsimultaneouslymeasuringgastricemptyingratesof liquidsandsolidswithsignificantiylessradiationburdento the patientthan the radioSdrthgraphictechnique.Methods: A test meal was used in which the liquid phase waslabeledwithtwomarkers,i.e.,3.7MBqof 1111n-DTPAand100mgof 13@g@ns@thesolidphasealsowasduallylabeledwith110 MBq of @c-atbur@ncol@dand 74 kBqof@acid.Simultaneousradiosdnbgraphicandbreath-testmeasurementswere performedin 27 subjects,10 normalcontrolsand 17

@entswithdyspepticsymptoms.Mathematicanatysisof theexcretion rate of labeled CO2 allowed the definition of four parameters,i.e.,the gasthcempt@ngcoefficlant,the gastrichaffemptyingtime,the peakexcretiontimeandthe lagphase.Resuits: Therewas a goodto excellentcorrelationbetweenthegastricemptyingcoefficientandthe scintigraphichalf-emptyingtime (r = 0.74 for liquids and r = 0.88 for solids), between thehalf-emptyingtime determinedby breathtest and the scintigraphichalf-emptyinglime (r = 0.91for liquidsandr = 0.92forsolids),betweenthe peakexcretiontimearidthe sdntigraphichalf-emptyingtime(r = 0.91for liquidsandr = 0.96for solids)andbetweenthelagphaseOtsolidemptyingdeterminedbybothtechniques (r = 0.89). ConclusIon: The duat carbon-labeledbreathtest is a valid,minimallyinvasivetechniqueto measurethe gastric emptying rate of both liquidsand solids.

Key Words: gastric emptying; breath test; radiosdrthgraphy;carbon-14-octanoicacid;carbon-13-glycine;indium-iI 1-DTPA;technetium-99m-albumin

J Nuci Med 1994; 35:824-831

he solid, liquid and oil phase of a meal are handleddifferently by the stomach and are emptied at differentrates. Accurate measurementofgastric emptyingin normaland pathologic conditions requires that these be measuredseparately (1—3).Radioscintigraphic techniques with twodifferent radionucides allow the measurement ofliquid and

ReceivedJul8,1993;revisionacceptedJan.26,1994.Forcorrespondenceorreprintscor*@Prct.Dr.P.Rutgeerts,Depaitmentof

MedicineandMedicalResearch,UniversityHospitalGasthulsbei@,B-3000Leuvan,B@m.

824 The Joumatof NuclearMedicine•Vol.35 •No. 5 •May 1994

Combined Carbon-13-Glycine/Carbon-14-Octanoic Acid Breath Test to Monitor GastricEmptying Rates of Liquids and SolidsB.D. Maes, Y.F. Ghoos,B.J. Geypens,0. Mys, M.I. Hide, P.J. Rutgeertsand 0. Vantrappen

Depart@nentofMedicüze@Division of Gastroenterolgy and Gastrointestinal Research Centtr, University HospitalGasthuLtheig; and Department ofMathematics, Leuven@Belgium

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(99%enrichment;Isotec,Miamisburg,OH) and3.7MBq of “InDTPA (Ultra Technicow). The total caloric value of the test mealwas 250 kcal.

MeasuringTechniquesTo measurethe retention of the liquid and solid phasein the

stomach, each subject was seated between the two heads of adual-headedgammacamera,equippedwithparallel-holelow-energy collimatorsand interfacedto a computer. Scanningscintigraphicinformationwas obtainedevery 10 mmup to 1 hr andeveiy 15 mm for another 1 hr. The liquid and solid still present inthe stomach at each scanningperiodwere expressed as retention,i.e., as the percentage of the activity of “Ininitiallyand @‘Tc,respectively, present. The activity present immediately after ingestion of the meal was taken as 100%.

Breathsamplingfor @3@o2and14(@()2measurementsfollowedthe same time schedule as the scintigraphictechnique but lastedanother2 hr of samplingat 15-mmintervals. For ‘3C02measurements, breath was collected in a 3-1 aluminum-coatedballoon(Tesseraux, Bürstadt,Germany). The ‘3Cbreath content wasdetermined by isotope ratio mass spectrometiy (FinniganMAT250, Bremen, Germany) or by on-line gas chromatographic punfication-isotoperatio mass spectrometry(ABCA,Europa Scientific,Crewe,UK). The C°2inbreathwas collectedby blowingthrough a pipette into vials containing 2 mmole of hyamine bydroxideuntil decolorationof the thymolphtoleineindicator,correspondingto the capture of 2 mmoleof CO2.The 14(@()2wasmeasuredby beta scintillationcounting.For both carbon labels,

@2production was assumed to be 300 mmole/m2 ofbody surface

per hour. The body surface area was calculatedby the weightheightformulaof Haycocket al. (7). Theresultsof the‘3C02and‘4cO2breath test were expressed as the percentage @3CO2and‘4c02,respectively,excretedperhourbycalculatingproceduresdescribedelsewhere(8).

Data AnalysisThe data obtainedby radioscintigraphicmeasurementwere

fitted by the modifiedpower exponential formulaof Siegel et al.(9). Half-emptying time (t1,,@)was calculated according to thefollowingformulaby SAScomputerprogram(PROCNUN) (10):

y = 1 —(1 —@

where y is the fractionaldose of “Inor @Tcstill retainedin thestomach comparedwith the initialdose; t time in hours;andk andp are constants. The half-emptying time is given by followingequation:

t1p_5 (1/k)@ lfl(1 _ 2@1@).

The lag phase of the solid phase was calculated as the first5%ofactivity (@“Tc)evacuated out of the stomach and expressed as:

/i@flag8= @i@)•ln(1 —0.05@―@).

The data obtained by breath test were fitted by two mathematicformulas using the least-square procedure. The best fit was retamed. The first formulais givenby

(I) y = at1'e@,

where y is the percentage of ‘3C02or ‘4CO2excretion, respectively, in breath per hour; t is time in hours; and a, b and c areconstants.Thesecondformulais expressedas

(II) y = mkfle@'(1 —e@')@ Eq.5

wherey is thepercentageof ‘3C/'4Cexcretioninbreathperhour;t is time; m, k and@ are constants; and m is the total cumulative‘3c/'4crecoveiywhentimeisinfinite.Thisformulaisthefirstderivativeof themodifiedpowerexponentialformulaof Siegeletal. (9) with a correction factor m. Nonlinear-regressionanalysiswas performed using the least-squares method by NONUN program (SAS, Raleigh, NC) (10) or a computer programwritten inExcel 4.0 for a 80386T computer (Mys 0, personal communication, 1992).

Threeparametersof gastricemptyingof liquidswere calculated.Firstis thegastricemptyingcoefficient(GEC),corresponding to ln(a)ofthe first formula and a global indicator for the gastricemptyingrate.Thesecondis thet,,,,@,thebreath-test-determinedgastrichalf-emptyingtime,calculatedby numericintegrationinthe firstformulaor by the followingequationusingthe secondformula:

t1p@_, (1/k)@ lfl(1 Eq.6

Thevalueof the best-fluedcurvewas retained.Thethirdis thepeak 13@ (‘4@f@)excretion time, he., the time of maximal‘3C02(l4@fJ@)excretionof thefittedcurve,calculatedby followlagequationderivedfromthefirstformula:

tmax b/c,

orby the followingequationusingthesecondformula:

tmax ln(@)/k.

Eq.7

Eq.8

This point corresponds to the time of maximal gastric emptyingrate.Thevalueof thebest-fittedcurvewas retained.

Thelagphaseof thesolidphasewas calculatedas thefirst5%of ‘4C02ofthe totalamountexcretedusingnumericintegrationinthe first formulaor following equation for the second formula:

tlag@= (1/k) . h@(1—@

Again, the value of the best-fittedcurve was retained.

Eq.9

Statistical EValuatIOnof ResultsEq. 1 The relationshipbetween the scintigraphicallymeasured half

emptyingtime(t,,,@)andthelagphase(tlag.)andthedataobtainedby breath-sampleanalysis [(GEC),half-emptyingtime (t,,,@),peakexcretion time@ and lag phase (tlag,j] were evaluated bycorrelation and linear-regression analysis (PROC CORR andPROC REG, SAS) (JO). The breath-test-determined half-empty

@ 2 ing times and solid lag phases were compared with the scinti1.Aj. graphically determined half-emptying times and solid lag phases

usingpaired-comparisonst-tests (PROCMEANS,SAS)(10).

RESULTS

Uquid PhaseFigure 1 shows the gastric emptyingrate of liquidsmea

sured by the two techniques in three typical examples.Figure 1A represents the 13(yJ2excretion curve of a subject with rapid gastric emptying rate (t,,,@= 18min); FigurelB shows the breath-test data of a subject with normal

Eq. 4 gastric emptyingrate of liquids (t1,,@= 47 min); and Figureic showsa delayedgastricemptyingpattern(t1,,@= 148mm). The solid lines represent the curve fitting;the circlesrepresent the breath-test data. These figures clearly show

Eq.3

BreathTestfor GastricEmptyingof UquidsandSolids•Maeset at. 825

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that increasing radioscintigraphichalf-emptyingtimes corresponded to characteristic changes in the ‘3C02excretioncurves. The inclination of the ascending part and the dcclinationof the descending partof the curve decreased, andthe peak of curve 1C was both diminished and delayed.

In Figure 2, the scintigraphicallymeasured half-emptying time is comparedwith the gastric emptying parametersdetermined by breath test. In Figure 2A, the relationshipbetween the scintigraphically and breath-test-determinedhalf-emptying time (t,,,@versus t1,,@)is shown. The comelation coefficient between the two parametersis 0.91 (p <0.0001). Linear-regression analysis results in the followingequation t,,,@= 70 + 0.97 x t@. This regression line hasa slope of nearly 1 with an intercept of the regression lineat time zero of 70 min. Using this regression model, thebreath-test-determined half-emptying times can be recalculated to the scintigraphically determined half-emptyingtimes. Paired-comparison t-tests showed no significant difference between these “corrected―breath-test-determinedhalf-emptying times and the scintigraphically determinedhalf-emptying times (p = 0.8355). Figure 2B illustrates therelationship between the scintigraphically determined gastric half-emptying time (t1,,@)and the peak excretion time(tmax). The linear-regression line between these two parameters is given by L..@= 45 + 0.95 x@ with a correlationcoefficient of 0.91 (p < 0.0001). Figure 2C shows the relationship between the scintigraphically determined halfemptying time and the GEC; the regression line is cxpressed by GEC = 3.50 —0.013 x@ with a correlationcoefficient r = 0.74 (p < O0001). Figure 3 displays thecorrected breath-test-determined half-emptying times, using the regression model.

Table 1gives the normalvalues of the 10healthy controlsubjects examined in this study of the scintigraphicallydetermined half-emptying time and the three breath-testdetermined parameters.

Solid PhaseFigure 4 illustrates the gastric emptying rate of solids in

three typical examples. Figure 4A shows the ‘4C02excretion curve of a subjectwith a rapidemptyingrate (t,,,@= 39min); Figure 4B represents a normalgastric emptying pattern (t1,,@= 69 miii); Figure 4C shows a delayed gastricemptying rate (t@ = 131 mm). The circles represent themeasured data, with the solid lines, the fitted curve. Cornpanisonof the different ‘4C02excretion curves for gastricemptying of solids indicates that the ascending and descending slopes of the curves diminish and that the peakexcretion of CO2°c@'@later and is slower with increasing scintigraphicallydetermined half-emptyingtimes.

The relationship between the scintigraphically determined gastric half-emptying time (t@) and the breath-testdetermined half-emptying time (t1,,@)is given in Figure 5A;the correlationcoefficient is 0.92 (p < 0.0001). The linearregression line between these two parameters is given bythe equation t,,,@= 74 + 1.04 x@ This line parallels thebisectrice, which allows easy recalculation of the scinti

00

1.00 2.00 3.00 4.00

@h)

10.00

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6.00

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C

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@h)

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FIGURE 1. Resuftsof the 1@C-gtycinebreathtest inthreetyploalcases.(A)A rapidgastricemptyingpattern(t1,@= 18mm).(B)Anormalgastricemptyingcurve(t1,@= 47mm).(C)Adelayedgastticemptyingpattern(t1,@= 148mm).

826 The Joumatof NuclearMediane•Vol.35 •No. 5 •May 1994

A

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0.00

B

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120

t112$tl/2bC°@t112@,(mm)GEC (mm)(mm)(mm)

I

I

2.50

tip_s = sdntlgraphically determined gastric half-empt@,1ng time; t1,@ =

breatMest-detenninedgastrichall-emptyingtime;t,,@= peakexcretiontime;GEC= gastricempt@ñegcoefficient.

180 0

@‘120A

U

0 60 120 180

tl/2s (miii)

0

1200

tlfls(mm)

B

FiGURE3. Comparisonbetween the sdntigraphicallydeterminedhalt-emptyingtimeandthecorrectedbreath-test-determinedhalf-emptyingtime,[email protected](solidline)betweenbothparametersusalsog@ien.

graphicallyhalf-emptyingtimes from the breath-test-determined half-emptying times using this regression model.Figures 5B and 5C represent the relationshipbetween thescintigraphically determined half-emptying time (t1,@)andthe breath-test-determinedpeak excretion time (t,@@)andGEC, respectively.The regressionlinescorrespondto thefollowing equations:@ = 41 + 0.83 x@ (m= 0.96, p <OMOO1)and GEC = 3.98 —0.01 x t,,,@(r = 0.87, p <0.0001). Figure 5D illustrates the relationshipbetween thelag phase of solid emptying determined by both techniques.The regression line corresponds to tlag,, = 26 + 0.82 xtla&; the correlationcoefficient between both is 0.89 (p <0.0001). Figure 6 represents the corrected values of thebreath-test-determined half-emptying time@ theywere not statistically different from the scintigraphicallydeterminedhalf-emptyingtimes (p = 0.9991)with a regression line expressed by@ = 1.00 x t,@.

In Table 2, the primaiy descriptive statistics are givenfor the different scintigraphically and breath-test-determined gastric emptying parameters of the 10 normalhealthy control subjects used in this study.

TABLE IMean, s.d. and s.e.m. of the ScintigraphicallyDetermined

Half-EmptyingTimeandtheThreeBreath-Test-Deterrr@nedParametersfor the Liquid Phase for the 10 Normal Control

Sub@

240

120

60

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60 120

tI/2s (mm)

0

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FiGURE 2. Compañsonof the radloSdntlgraphicallydeterminedhalf-emptyingtime with the breath-test-determinedparametersforthe liquidphase:the half-emptyingtime (A),the peakexcretiontime(B)andtheGEC(C).Alsotheregressionlines(solidlines)betweenthe Sontigraphicallydeterminedparametersand the breath-testparametersare given.

Mean38.43.03105.036.172.0s.d.18.20.4719.620.238.4s.e.m.5.80.156.216.412.0

827BreathTest for Gastiic Emptyingof Liquidsand Solids•Maes et at.

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These results indicate that the breath tests described inthis article allow the measurement of gastric emptying ofsolids and liquids with an accuracy similar to that of radioscintigraphy. As in radioscintigraphictechniques, emptying of the solid phase of a meal can be measured simultaneously with liquid emptying. To demonstrate this, aquadruple-labeledtest meal was used with ‘3C-glycineand“In-DTPAlabeling the liquid phase and ‘4C-octanoicacidand @“Tc-albumincolloid marking the solid phase. Thistype of test meal is considered a standard test meal forscintigraphic gastric-emptying studies. By simultaneousmeasurement of the retention of scintigraphic markers inthe stomach andthe excretion oflabeled CO2in breath, thetwo techniques can be accurately compared.

The breath-testmarkersused to measure gastric emptying were ‘4C-octanoicacid for the solid phase and ‘3C-glycine for the liquid phase of the meal. The ‘4C-octanoicacid breath test was validated in another study by simultaneous radioscintigraphic measurement of @‘@Tc-albumincolloid and the analysis of 14@yj2excretion in breath afterthe intake of solid test meal, labeled with both @“@Tcalbumin colloid and ‘4C-octanoicacid. Octanoic acid was agood marker for the solid test meal used, with a rapidduodenal absorptionand hepatic oxidation; the breath testshowed a good correlationwith the scintigraphictechniquefor all determined gastric-emptying parameters (6).Glycine was selected as marker of the liquid phase becauseit is easily soluble inwater (11). It is postulatedthatglycineis not absorbed in the stomach; the site of absorption ofglycune and other neutral amino acids is located in theproximal intestine, using mainly active transport mechanisms (12). After transport across the intestinal wall,glycine is partly oxidized to CO2 by different pathways(13,14).

Although the carbon-labeled glycine and octanoic acidbreath tests are indirect methods to measure the gastricemptying rate of liquids and solids, respectively, mathematic analysis of the labeled CO2excretion curves allows adescription of the liquid and solid emptying rate in muchthe same way as the radioscintigraphictechnique.

The breath-test-determined half-emptying time correlates well with the scintigraphically determined haif-emptying time. The regression line between these two parameters has a slope of nearly 1, with the point of intersectionwith the y-axis lying at ±70miii. This delay between thescintigraphically and breath-test-determined half-emptyingtime, calculated by regression analysis, is almost identicalfor both glycine and octanoic acid. This observation indicates that differences in absorption, metabolism and excretion of the two markers are minimal. Recalculating thebreath-test-determinedhalf-emptying times, corrected onthe basis of the regressionmodels, results in values similarto those obtained by radioscintigmaphy.

The peak excretion time, defined as the time of maximallabeled CO2 recoveiy of the fitted curve, is related to the

A

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0.00@ t , [email protected]..•---..------4

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FiGURE 4. Resultsofthe 14f@@@ breathtestinthreetyp@alcases. (A)A rapidgastñcemptyingpattern(t1,@= 39 mm).(B)Anormalgasthcemptyingcurve(t@ = 69mm).(C)A delayedgasthcemptyingpattern(t1125= 131mm).

828 The Joumat of Nudear Medicine•Vol. 35 •No. 5 •May 1994

DISCUSSION

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tias(h)

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60 120 180 240 300 360 420 4800 0 60 120 180 240 300 360

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FIGURE 5. Compañsonof the radiosdntigrapt@caNydetermkiedhalf-emptyingtime withthe breath-test-determinedparametersforthesoid phase:the half-emptyingtime (A), the peak excretiontime (B) and the GEC (C). (D) The relationshipbetweenthe lag phasesdeterminedby both techniques.Also the regressionlines (solid lines) betweenthe SCIntIgraphICaIIydetern*@edparametersand thebreath-testparametersare given.

0

I60 1200

Usgs(miii)

labeled CO2 recovery of the fitted curve, is related to themaximal gastric emptying rate. Although this parameterhas a differentphysiologic meaningthan the half-emptyingtime, the peak excretion time correlateswell with the scintigraphicallydetermined half-emptyingtime, accepting anaverage delay between both parametersof 45 mm.

The good correlationof both the breath-test-determinedgastric half-emptying time and the peak excretion time withthe radioscintigraphic half-emptying time is probablycaused by the fact that these two breath-test parametersare, by the natureof their mathematicdefinition, independent of the endogenous CO2productionand the amountof‘3C-glycinethat is converted to CO2. These parameters areonly dependent on the shape of the CO2 excretion curve.Studies with ‘4C-glycineshow that the amount of glycinemetabolized to C°2may be reduced in some pathologicconditions, but the shape of the 14(@()2excretion curveremains unaltered (15). Moreover, despite the different

420

360

300

240

0

I

I0

0

0 60 120 180 240 300 360 420

tl/2s (miii)

FIGURE 6. Comparison between the scmntlgraphlcaltydeterminedhalt-emptyingtimeandthe correctedbreath-test-determinedhalf-emptyingtime,basedon the regressionmodel.The regressionline is representedas a solidline.

829BreathTestfor GastsicEmptyingof LiquidsandSolids•Maesat at.

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t112$= scmntlgraphically determined gastric half-emptying time; t1,@, =

breath4est-determinedgastrichalt-emptyingtime;t,,@= peakexcretiontime;GEC= gastricemptyingcoefficient

tabolized after absorption (as shown by the peak excretion[percent of the dose perhour]in the CO2excretion curves),regression analysis between the scintigraphically determined half-emptying time and the breath-test-determinedhalf-emptying time and peak excretion time resulted innearly the same regression lines for both markers. Thisfinding indicates that absorption, metabolism and excretionarenot the rate-limitingsteps in these processes. However,further validation is needed in the future in regard to metabolic diseases.

The GEC, althougha reliableindex for the global assessment of the gastricemptyingrateof liquidsand solids, doesnot correlatewell with the radioscintigraphichalf-emptyingtime. This may be partly caused by the fact that this parameter is dependent on the amount of labeled CO2 cxcreted and partlyalso by the fact that, invery rapidgastricemptying pauemns, this parameter can be underestimatedby fitting deficiencies (Fig. 1C). This, however, is not amajor disadvantage because visual control of the labeledCo2 excretion curve demonstrates that the fitted curveunderestimates the process in this subject.

The breath-test-determinedsolid lag phase, which is alsoindependent of the total amount of labeled CO2excreted,correlates well with the scuntigraphicsolid lag phase andtherefore gives additionalinformationon the early patternof gastric emptying of the solid meal.

Because the pattern of gastric emptying of liquids andsolids can be adequately described by dual-labeled CO2breath sample analysis, using biexponential models, thecombined ‘3C-glycineand ‘4C-octanoicacid breath testingcan be a valid alternativefor the radioscintigraphicmethodto monitor gastric emptying. The ‘3C-glycmnebreath testcompares favorably with other tests of liquid gastric emptying, e.g.. aspiration technique (16), radioscintigraphy(5), paracetamolabsorptiontest(17),theechographicmethod (18) and the recent MRI technique (19). Combinedwith the ‘4C-octanoicacid breath test, this dual-labelbreathtest may be a good alternativefor radioscintigraphyfor the simultaneousmeasurementof liquidand solid emptying.

Although lacking information about intragastric distribu

tion of the different phases of the test meal, breath-testmeasurementsofgastnic emptyingofferseveral advantagesover radioscintigraphictechniques. The combined breathtest is minimally invasive and exposes the patient to significantly less ionizing radiation than radioscintigraphy.The whole-body radiationwith the breath-test method isless than 0.015 mCiy (for 74 kBq of 14C-octanoicacid)compared with 078 mGy for the combined scintigraphictechnique (054 mGy for 110MBq of@Tc-albumin colloidand 0.24 mGy for 3.7 MBq of 11'In-DTPA)(20—27).Thisallows repeated emptying studies to be done in a shortperiod (e.g., detection of transient disorders, evaluation ofthe influence of therapeutic actions and evaluation of theday-to-day variability in the individual patient). In addition, breath tests are easy to perform, even for elderly ordisabled patients, and can be carried out at the bedside,with several tests being done simultaneously in differentpatients. Breath tests do not immobilize costly equipmentor dedicate an investigator's time for a single patientduringa considerable period. Breath samples can be analyzedafter completion of the sampling at a convenient time.Moreover, latest developments in isotope ratio mass spectrometiy also make ‘3C02measurements readily accessi

ble to clinical laboratories;in addition, breath tests can beperformed outside the hospital, because the labeled CO2samples can be sent to an analytic center.

In conclusion, the combined 13C-glycine/'4C-octanoicacid breath test is a safe and valid test for measuring thegastric emptying mate of liquids and solids simultaneously,thereby reducing radiationexposure to the patient.

ACKNOWLEDGMENTS

TheauthorsthankProf.M. Dc Roo,Dr.J.L UrbainandMissV. Vandenmaegdenberghfortheirhelpin performingtheradioscintigraphic examinations of gastric emptying and D. Claus, N.Gorris, S. Rutten and L. Swinnen for technical assistance. Thisworkwas supportedby grant3.0094.92,FWGO,Brussels,Belglum.

TABLE 2Mean, s.d. and s.e.m. of the ScmntigraphicallyDetermined

Half-EmptyingTime and Lag Phase and the FourBreath-Test-DeterminedParametersfor the SolidPhasefor

the 10 Normal Control Subjects

ti,2. tiag@ t112@, Corrected t1@2@,@

(mm) (mm) GEC (mm) (mm) (mm) (mm)

Mean61.716.903.29133.5168.2293.0037.96s.d.23.2111.290.3928.2627.1721.0810.81s.e.m.7.343.570.128.948.596.673.42

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831BreathTest for Gasthc Emptyingof Liquidsand Solids •Maes at at.

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1994;35:824-831.J Nucl Med.   B.D. Maes, Y.F. Ghoos, B.J. Geypens, G. Mys, M.I. Hiele, P.J. Rutgeerts and G. Vantrappen  Emptying Rates of Liquids and SolidsCombined Carbon-13-Glycine/Carbon-14-Octanoic Acid Breath Test to Monitor Gastric

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