Th. W. vander Mark,A. E. C. Rookmaker,A. Kiers,R. Peset,W. Vaalburg,A. M. J. Paans,andM. G. Woldring

UniversityHospital,Groningen,Netherlands

Due to the solubility of xenon-133 in blood and tissues, errors are Introduced inthe detomiination of rgional pulmonary ventilation. We investigated thees errorsby comparing the results from ventilation measurements with Xe-133 and N-13 infive normal subjects (both at rest and during exercise) and Inseven patients aftera pnumonectomy. in the normal subjects at rest, the upper lung fields showed nosignificant difference Inthe uptake rates of the two gases. Inthe middle and lowerlungfields,however,the uptake rate for Xe-133was higherthan forN-13.Duringexercise a significant increase of the specific ventilation was found in the upperlung fields for N-13 compared with Xe-133. in the pneumonectomy patients theoverall uptake rate for Xe-133 in the intact hemithorax was 25 % larger than forN-13. Over the pneumonectomized hemithorax the uptake of the fastest component of Xe-133 was (8.5 ±1.3)% of the total. The total chest-wall contribution ofXe-133 was (27 ±8)% of the total count rate.

J Nuci Med 25: 1175—1182,1984

VA00= VA+XQ

k = VA@VA

From a physiological point of view, nitrogen-13-la (4)]. For a soluble gas (see Appendix) theparametersbeledmolecular nitrogen is the most appropriate mabecome:dioactive

gas for regional ventilation studies, as was already pointed out in 1965 by Matthews and Dollery(1).(2)Due

to the short half-life of N-13 (T112= 10 mm),theavailabilityof this gas is limited to those centers withaandproductionfacility in the vicinity of the hospital.Forroutine

clinical tests, xenon-133 is most widelyused(3)becauseof the convenient half-life (5.3 days) andthewidespread

availability. .where Q denotes the regional pulmonary blood flow,VAComparedwith N-13, Xe-133 has disadvantages, ofthe regional alveolar volume, VAthe regionalventilation,which

the most serious is the solubility of xenon in bloodX the blood-gas partition coefficient, and f is a proporand tissues. The blood-gas partition coefficient, A, oftionality factor, depending on the efficiency of the dexenon is 0.15 (2). This is more than ten times the parti tectors. When X = 0, Eqs. (2) and (3) reduceto:tion

coefficient ofnitrogen [A = 0.014 (3)]. The fairly. . . .

high solubihty of xenon may cause severe errors in the@T

@@@@ .

1@ — I • @Aanu@ — VA/VA.4assessment

of regional ventilation.When nitrogen-13 and xenon-l 33 are used together,theThewashin of an inert tracergas duringspontaneousrelation between their k values can be givenas:breathing

has been described by Kety.(4). For everyregion of interest, Kety's model can be formulated as:kx@/kN = 1 + A. -@-. (5)

VAN(t)=N(1 (1)Here

the partition coefficient for nitrogen isneglected,Forthe case ofan insolubletracer, N. is proportionalsince it is less than 1/ioof AXe.From this equation itisto

regional volume, and k equals the regional specificclear that the ratio of the regional specificventilationsventilation[alveolar ventilation per unit alveolar volumeobtained with both radioactive gases depends upon the

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VAN DER MARK,ROOKMAKER,KIERS,PESET,VAALBURG,PAANS, AND WOLDRING

regional ventilation/perfusion ratio, with kX@> kN. Weshall refer to this as the “ventilation-perfusioneffect.―

A similarrelationcan be establishedfor the parameterN,.,. Since this parameter is expressed as percent of totalcounts over both lungs, we are left with the proportionality factor f, which is quite different for the gases used.Therefore N@,is less suitable for investigating the effectof the regional ventilation/perfusion ratio.

For the regionalventilation,derivedfrom the regionalparameters N,, and k as k.N,,, it follows from Eqs. (2),(3), and (4) that regional ventilation is not affected bythe regional ventilation/perfusion ratio. Another effectmay be important, however—thedissolved Xe-133 enters the systemic circulation and is transported to varioustissues throughout the body, including those in the chestwall. This activity is also seen by the detecting device. Ifwe assume that the appearance rate of Xe-133 in thechest wall is smaller than the specific ventilation, thenthe effect of this phenomenon on the measured k will becontrary to the effect of the ventilation/perfusion ratio.We will call this the “chest-walleffect.―

The effect of Xe-133 in the chest wall upon the parameter N,., corresponding to regional lung volume, willbe that for all regions of interest this parameter comesout too large, depending also on magnitude and entryrate of Xe-l 33 into the chest wall.

To estimate the errors caused by both the ventilation-perfusion effect and the chest-wall effect, we performed experiments with normal subjects at rest andduring exercise, the latter because during exercise theventilation/perfusion ratio is increased (5). To obtaininformation about the chest-wall contribution, we alsostudied postpneumonectomy patients.

SUBJECTS AND METHODS

We have studied regional ventilation in five normalsubjects and in seven patients who had undergonepneumonectomy, using both Xe-l33 and N-13. Informed

@ consent was obtained from all participants. Normalsubjects, all males, were defined as normal on the basisof a negative history with respect to chronic airway obstruction, and normal spirometric values. The mean agewas 35 yr (range 30-43).

The postpneumonectomy patients, also males, were,selected to have minimal radiological signs of herniationof the remaining lung. As a criterion for minimal herniation we accepted only patients in whom the chestradiograph showed no air-space between the edge of thespine on the operated side and the contralateral boundaryof the trachea. The mean age of the postpneumonectomypatients was 60 yr (range 49-68). The average timebetween operationand the investigation was 5 yr (range2-10). One patient had the pneumonectomy for a lungdestroyed by tuberculosis. The others underwent a curative resection for planocellular carcinoma. All patients

were heavy cigarette smokers until their operation.Spirometric values were considered “normal―when thedecrease in vital capacity (VC) and forced expiratoryvolume in one second (FEV1) was in accordance withsurgical loss of lung tissue. Average spirometric valueswere: VC = 53% predicted, FEV1 55% predicted,FEV1/VC = 69%.

A spontaneous breathing method was used, as described earlier (6—8).The subjects were connected to a“bag-in-box―system to ensure a constant inspiratoryconcentration of Xe-133 (0.1 mCi/l = 3.7 MBq/l) orN-13 (0.2 mCi/l = 7.4 MBq/l). Due to the differentgamma energies, the two radioactive gases could not bemeasured simultaneously—the 80-keV emission ofXe-133 would be obscured by the severe Comptonscatter from the 51l-keV annihilation radiation of N-l3.Therefore, an initial determination was performedwithN-13, and after 1-2 hr the same procedure was repeatedwith Xe-133.

Xenon-133 was obtained commercially. Nitrogen-I 3was produced by bombarding a water target with 20-MeV protons, by the reaction ‘60(p,a)'3N.After irradiation, the ‘3NO@formed was reduced to ‘3NH3withDevarda's alloy in alkaline solution, and the ‘3NH3wascollected by distillation (9). In the lung function laboratory, carrier NH3 was added to the solution, then anexcess of NaOBr. The evolved N-13-labeled N2 gas wastransferred into the bag-in-box system.

Recording was performed with multiple detectors, sixin front and six at the back of the subject. The detectorswere l@X I@NaI(T1) scintillation crystals with a resolution of 10% at the 660-keV Cs-137 energy. Eachcrystal-photomultiplier combination was surrounded bya cylindrical lead collimator 9 mm thick, with 45 mmbetween the front of the collimator and the entrancewindow of the crystal. For the experiments with N-l3,an extra cylindrical lead collimator, 15 mm thick, wasattached. The relative efficiency of the detectors wasdetermined by recording the radiation emanating froma flat phantom, filled as needed with a solution of Xe-133in saline or a solution of the 68-mm position emittergallium-68 (from a Ge-68 —÷Ga-68 Ga generator elutedwith EDTA. For Xe-133 only the energies above 75 keVwere recorded;for N-13 only those above 450 keV. Detectors were placed halfway between the midline and thefirst axillary line, with three detectors covering each lung.The detector for the upper lung fields was placed 1 cmbelow the clavicle, for the lower lung fields 1 cm abovethe anterior lower lung boundary as determined bypercussion; the middle detector was halfway between theupper and lower detectors. The detectors at the backwere aligned with those at the front of the subject. Thecalculated volume and ventilation percentages of thecorresponding anterior and posterior detectors wereadded and the calculated k values for these detectorswere averaged. Background was determined during 1

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mm preceding the inhalation of the radioactive gas-airmixture. The washin period lasted 5.5 mm and thewashout 3.5 mm. The activity was recorded in 6-sec intervals and the results were stored for subsequent cornputer analysis.

The procedure for the measurements with exercisewas different. Because of its inertia the bag-in-box systerncould not be used. Thereforea 6-1anesthesiaballoonwas connected through a three-way valve to the subject,who was seated on a bicycle ergometer. After equilibration, measured by monitoring the helium concentration in the balloon, the inspiratory side of.the valvewas switched to room air, thereby starting the washoutof the radioactive gas. Expired gas was collected inDouglas bags, and, in the case of xenon-i 33, absorbedinto a xenon trap (10) to avoid radioactive contaminationof the room air. In this setup most of the backgroundradiation was caused by the activity in the balloon. Sincethis varied during the measurement, we recorded theballoon activity with a separate detector, mounted so thatit could not see the activity in the subject's lungs. Beforethe inhalation of the radioactive gas mixture, the balloonactivity was measured both by the detectors monitoringthe lung and by the balloon monitor, with the subject inplace. The ratio between the count rate of each of thelung detectors and the balloon monitor is then a measureof how much of the balloon activity is seen by the lungdetectors. The recording of the balloon activity duringthe measurement, multiplied by this ratio, yields abackground curve for each of the lung detectors, whichwas subtracted from the gross recording of each lungdetector.

With this setup four normal subjects were measured,both at rest and during exercise. The exercise measurements were started after 3 mm of cycling at 100 W, inorder to ensure that the subject was in a steady state.

Counts measured in the N-i 3 experiments were corrected for decay before analyzing the data. Analysis wasperformed in terms of Kety's model [Eq. ( 1)] , but withthe additionofan extraquadratictermto the exponentialmodel. From the work of Susskind (1 1) we know thatthere are a number of very slow components in thewashin curve, the fastest having an exponential constantof 0.2 min1 . By adding an extra quadratic term to themodel equation, these components are removed. Themodel equation then takes the form:

N(t) = N.,(i —e@t)@ ao + a1t + a2t2 (6)

The calculation of the parametersN@and k [Eq. (1)]was performed by a nonlinear least-squares techniquewhose details have been described earlier (12). For theexercise experiments the program was modified to treatthe washin and washout exponential constants separately, since rebreathing causes these exponentials todiffer considerably. The washout was used for the specific ventilation.

The values foundfor N.,, for the differentlung regionsare converted to “volumepercentages―for each lungregion by dividing the regional value found for N by thesum of the values of N for all regions. In this way theproportionality factor f [Eq. (2)] was removed. The sameprocedure was used for the regional ventilation, k.N@,to obtaina “ventilationpercentage―foreach lung region.For statistical comparisons the paired t-test was used.

RESULTS

Normal subjects at rest. In normal subjects at rest wefound a good correlation (r = 0.88) between the volumepercentages measured with the two radionuclides. This

could be expected since these subjects had essentially anormal distribution of lung volumes. However, thereseems to be a slight tendency,not statisticallysignificant,for the distribution of lung volumes measured over thethorax to be more uniform with Xe-133 than withN-13.

To comparethe specific ventilations[k in Eq. (1)], wetreated upper, middle, and lower parts of the lung separately because the ventilation perfusion ratio variesfrom apex to base (5, 13). In the upper lung fields wefound no significant differences in the specific ventilation. The average difference was 0.24 ±0.18 min1, (t= 1.36, n = 9, n.s.). In the middle and lower lung fields,

however,we founda significantdifferencein the specificventilations, the value for Xe-i33 being the larger one.The results for the middle lung fields are: average difference 0.44 ±0.17 min', (t 2.55, n = 9, p < 0.025),and for the lower lung fields: average difference 0.55 ±0.29 min1, (t = 1.90, n = 9, p < 0.05). These results aregraphed in Fig. 1. For statistical comparison the pairedt-test was used. An excellent correlation (r 0.91) wasalso found for the values of the specific ventilations,measured with both tracers.

specific

upper lower

FiG. 1. Valuesof specificventilationin normalsubjectsat rest,measured with Xe-133 and N-13 for various lung fields. Extensionsrepresent s.e.m.

Volume 25, Number I 1 1177

VAN DER MARK, ROOKMAKER, KIERS, PESET, VAALBURG, PAANS, AND WOLDRING

K (min1)

10@

8

Rest Exercise

I

J

Xe-133

N-13

I

6

2

A

Normal subjects during exercise. The results for normal subjects at rest, mentioned above, have been confirmed by measuring normal subjects at rest in themodified setup for measurements during exercise,thereby indicating that the two setups gave comparableresults (Fig. 2). During exercise (3 mm, 100 W) thepicture changed drastically. Apart from an almostthreefold increase in overall specific ventilation, thespecific ventilation obtained with Xe-i33 in the upperparts of the lungs is significantly smaller than the valuesobtained with N-13 (average difference 1.32 ±0.52min', t = 2.55, n = 7, p < 0.025). In the middle andlower parts of the lungs no significant differences inspecific ventilation could be established (Fig. 2).

Patients after pneumonectomy. Typical ventilationcurves from a patient who had had a pneumonectorny are

shown in Fig. 3. On the pneumonectomized side wemeasured a volume percentage with Xe-133 of (12.6 ±l.0)%. The value found using N-l3 was (4.1 ±0.8)%.(Both are average ±s.c.m.) The values for the specificventilation in the intact hemithorax were also higher withXe-133 than with N-13. No difference could be observedbetween upper, middle, and lower parts of the remaining

lung. The average difference was 0.40 ±0.09 min@ (t= 4.25, n = 20, p < 0.005, Fig. 4). The uptake rate for

Xe-i 33 on the pneumonectomized side must be considered the tracer's uptake rate in the chest wall; this equals0.72 ±0.07 min@.

DISCUSSION

In previous experiments (Preset R, van der Mark

Th.W., Beekhuis H, unpublished data) we tested thevalidity of sequential measurements by performingduplicate determinations with Xe-i33. We found an average differencein the k valuesof0.03 ±0.07 min@, anda very high correlation between the values for N@(r =0.99). We therefore concluded that comparison of twodeterminations performed successively was justified.

As already mentioned in the introduction, the solubility of xenon introduces two effects: the “ventilationperfusion effect―and the “chest-walleffect.―In normalsubjects at rest, these effects seem to cancel each otherin the upper lung fields, since there is no significantdifference. In the middle and lower lung fields, the kvalue is significantly higher for Xe-i33 than for N-13(Fig. i). This is understandable because there is lessperfusion in the lung apex, so that the effect of the yentilation/perfusion ratio is smallest in the apex. The

@ ventilation/perfusion ratio decreases towards the lungbase, therebyenhancingthe firsteffect mentionedabove,so that the difference between the Xe-133 k value andthat with N-i3 increases towards the lung base.

Under exercise the overallventilation/perfusion ratioincreases by a factor of @‘@.‘2(5, 13). Also, according to

Harf (5) and West (13), the gradient in the ventilalion/perfusion ratiofromapex to basedisappears,so thatthe ratio is distributed more evenly over the lung. Consequently, the term containing the ventilation/perfusion

ratio [XQ/VA in Eq. (5)] becomes less important.Thereforethe differencebetweenthe k values forXe-133and N-13 should decrease, relative to the values at rest.Our results for the middle and lower lung fields show

1178 THE JOURNAL OF NUCLEAR MEDICINE

nnnnnUpper Middle Lower Upper Middle Lower

FiG. 2. Values for specific ventilation in normal subjects at rest and during exercise. Extensions represent s.e.m.

.-@--- @—

CLINICAL SCIENCESDIAGNOSTICNUCLEARMEDICINE

R L

N2(lower).In each frame, numberof

Xenon-133

Anterior Posterior

UPPER

MIDDLE

LOWER.J_-@

—Nitrogen-13UPPER

MIDDLE

LOWERPosterior-•@

@•--.--

@@ -.. @----.--@--

.---@ ---@---

---

R L R L

Anterior

R I

FiG. 3. VentIlation curves from left pneumonectomy patient, using Xe-133 (upper) and [N-13]normalized counts has been plotted against tIme. Total duration of one study is 10 mm.

that at rest the k value for Xe-133 is significantly largerthan that for N-13, whereas this difference disappearsduring exercise. This finding confirms the theory outlined above, at least for the middle and lower lung fields.For the upper lung fields, however, we observe that thek for N-i3 is the larger one. This may indicate that thechest-wall effect is the prevailing one in these circumstances. If we assume that the chest-wall effect is distributed essentially homogeneously over all lung fields,we must conclude that during exercise the ventilation/perfusion ratio is not evenly distributed, in the sense thatin the upper lung field the ventilation/perfusion ratio islarger than in the middle and lower lung fields. Thisconclusion conflicts with other findings (5, 13). An cxplanation may be that in the other investigations regionalventilation and regional perfusion were measured separately, with the former measured by inhaling radioactive gases, and the latter by administering the radioactivetracer intravenously. The alveoli that are reached by

inhalation are not necessarily the same as those reachedby the intravenous route. In our case, however, bothtracers are inhaled, and the ventilation/perfusion ratioenters the equations because of the solubility ofxenon.

In the pneumonectomy patients we also found a difference in k values in the intact hemithorax, with k uniformly distributed over that side. Since it is known thatthe total pulmonary blood flow after pneumonectomyis not significantly reduced ( 14), it is possible that theupper field of the remaining lung receives a relativelylarger part of the pulmonary blood-flow, making theventilation/perfusion ratio more evenly distributed overthe remaining lung. This could be the reason why nosignificant differences are seen between upper, middle,and lower parts.

Concerning the uptake rate of Xe-i33 in the chestwall, the component with an exponential constant of 0.72±0.07 min@, has not beenfound by Susskind (11). This

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VAN DER MARK,ROOKMAKER,KIERS,PESET,VAALBURG,PAANS, AND WOLDRING

specificventilation(mm-i)

upper middle lowerFiG. 4. Values of specific ventilation in pneumonectomy patients.Extensions represent s.e.m.

can be explained by the fact that, measuring over thelungs, this component is masked by the lung washinconstant, which in normal subjects is about 2-3 times aslarge, and has a much larger range. Thomasson andClark (15), using advanced numerical techniques, havedemonstrated that the separation of exponentials waspossible when the ratio was 2:1. With greater scatter inthe data, the resolvability would be less, which may bethe reason why this component was not observed bySusskind et al. (1 1). In studies of regional cerebral bloodflow, a component in the same order of magnitude hasbeen found after inhalation of Xe-i33 (16).

We investigated how this chest-wall washin influencesthe measured specific ventilation. For this purpose weconstructed curves to simulate the washin of a radioactive gas. First we analyzed the curve to see whether theinput values for specific ventilations were recovered.After that we added to the simulated curve a single cxponential with exponential constant equal to the numberfound for the chest-wall entry rate (0.72 min'), andperformed the analysis again. We found that if thischest-wall curve contributes iO% to the total curve, themeasured k value will decrease by 8%over a wide rangeof k values. To compare this figure with our results, wetook from the work of Harf (5) the ventilation/perfusionratios of 1.67, 0.93, and 0.73, respectively, for the upper,middle, and lower lung fields (at rest), and calculatedwith Eq. (5) the percentage increase for the xenon kvalues compared with the nitrogen k values of 9, 16, and21%, respectively. Since we found no significant difference in the upper lung fields, the chest-wall componentmust compensate for the 9% increase of the xenon k

3

2

1

Xe-133 Xe-133 Xe-133

FIG.5. Radiographof pneumonectomy patient in Fig. 3, showingdisplacementoftrachea.

value; this figure agrees very well with the simulationstudies and with the uptake percentage of Xe-l33 foundfor the pneumonectomized side in the patients. For themiddle and lower lung fields, the estimated increase ofthe Xe-i33 k value was somewhat smaller than measured, but in view of the experimental errors and theimprecision of the ventilation/perfusion ratios, theagreement is still fair.

A detailed quantitative comparison for the valuesfound at exercise is not possible, although the qualitativeagreement is adequate. It can be expected that thechest-wall uptake rate during exercise is faster than the

value found at rest, due to increased tissue blood flow.Although the patients were selected to have minimal

radiological signs of herniation of the remaining lung,displacement of the trachea had always taken placetowards the pneumonectomized side (Fig. 5). Wetherefore assume that the 4. 1%, found on the operatedside with N-13, must be due to the trachea because partof the trachea is seen by the detectors. This is stronglysupported by the fact that with N-i3 we found a veryrapid uptake rate of 5.2 ±i.7 min@. This is an indication that the “volume―seen on the operated side is arapidly ventilated compartment, as the trachea must be.Since the detector geometry was not changed betweenthe investigations with the two gases, the difference in“volumepercentage― between them on the pneumonectomized side is therefore due to uptake of Xe-l 33

in the chest wall. For one hemithorax this appeared tobe (8.5±i.3)%.

In the discussion so far we have considered only the“chest-walleffect,―responsible for the fastest componentof the uptake into the chest wall. With our method of

analysis (12), components with exponential constants

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CLINICALSCIENCESDIAGNOSTICNUCLEAR MEDICINE

VA O@ VA+XO@@ VA

smaller than 0.2 min@ do not influence the results for@ and k obtained from the least-squares analysis, since

the slow components are removed by the quadratic termin the model equation. To obtain the total chest-wallcontribution, all components should be included. Fromthe constants ao, a1, and a2 [Eq. (6)] describing thewashin of the slow components, we estimate the contribution of these components as (i8.5 ±7.5)% of the totalcount rate, so that our estimate for the total chest-wallcontribution is (27 ±8)% of the total count rate. Thisfigure agrees well with our earlier estimate (17) and alsowith the value of 30% reported by Brusasco (18). FromXe-i 33 experiments in dogs, Rhodes and co-workers(19) estimated, a chest-wall contribution in the range10-20%.

In analyzing the N-l3 data, we note that the constantsa0, a1, and a2 did not differ significantly from zero. Fromthe difference in blood-gas partition coefficients, onewould expect the contribution of the slow componentsto be ‘@‘10times smaller for N-13-labeled gas than forXe-l33. Our results show that it is certainly less than 1/so.but we were not able to assign a value different from zerofor this contribution.

The method of analysis to remove the slow components from the washin curve appears to be advantageous.Without such a procedure, the chest-wall washin curveis a combination of several exponentials, including veryslow ones. The analysis of such a curve as a single cxponential results in a much lower entry rate for chestwall washin, as found by Brusasco (18), who also studiedpneumonectomy patients. The same reasoning may beapplied to explain the results of Ronchetti et al. (20). Theassumption of 90% elimination strongly overemphasizesthe slow components of the washout curves.

In conclusion, the results of the present investigationshow that the gradient in specific ventilation from theupper to the lower regions of the lung, found with Xei33, is due mainly to the ventilation/perfusion ratio.During exercise the ventilation/perfusion ratio in themiddle fields is approximately equal to that in the lowerfields, whereas that in the upper fields is higher. Inpneumonectomy patients we observed an evenly distributed ventilation/perfusion ratio over the remaininglung. The amount of Xe-i 33 accumulated in the chestwall is (27 ±8)%. Of this figure 8.5% is due to a relativefast component. The correction for the chest-wall activitytherefore depends on the method of analysis. When slowcomponents are corrected for in the analysis of thewashin curve, only a small correction is necessary. Whenthese slow components are not removed, the correctionfor chest-wall activity may be substantial.

The appearance of a relatively fast chest-wall cornponent (k = 0.72 min') may have serious consequencesin studies of patients with chronic airway obstruction,in whom the specific ventilation is reduced. Here the use

of N-13-labeled N2 should be of great advantage.

ACKNOWLEDGMENTS

We thankProf.Dr. HJ. Sluiterforthe opportunityto studypatientsfrom the Departmentof Lung Diseases, the lung functiontechniciansfor their helpin collectingdata, the cyclotronstaffof the KernfysischVersnellerInstitutforoperatingthecyclotron,andMissY.H.Werkhovenfor typingthe manuscript.This investigationwassupportedin part by the Foundationfor MedicalResearch,FUNGO, whichissubsidizedby the NetherlandsOrganizationfor the AdvancementofPure Research(Z.W.O.).

APPENDIX

Accordingto Kety(4), the followingdifferentialequationdescribes the exchange of an inert gas in the lungs:

dMA VA dFA VA(FI —FA) +@ —Ca), (7)

where MA is the amount of inert gas in the alveoli, VA is the alveolarvolume,FAis the alveolarconcentrationof the inertgas,F1is the inhaledconcentrationofthegas,VAisthealveolaryentilation rate,@ the rate of pulmonary capillary blood flow and C,,and Ca are, respectively, the mixed-venous and arterial concentrations of the inert gas.

Forthecaseofsaturationwithan inertgas,whereFA= 0 andCa 0 at t = 0, the solution of Eq. (6) is given by

FA A1F1(1 —ekt) + A2ektfC,,e@dt, (8)with

(9)

and

O=1_e@'S/@, (10)

where D' is the diffusion coefficient for the gas across the alveolarmembrane, and S/@ is the ratioof diffusion surface to volume flowof blood for the capillary or the lung as a whole. In most cases 0isnearlyequalto unity.Kety(4) givesanextensivetreatmentforthe term containing the mixed-venous concentration [second termin Eq. (7)]. According to that view, it appears that this term doesnot contributesignificantlyto the alveolarconcentrationof theinert gas, provided that the partition coefficient Ais not too large,which is certainly the case for xenon. If, therefore, the second termineq.(8) isomitted,and0 istakenas 1,thepreviouslygivenEqs.(2) and (3) result directly from Eq. (9).

REFERENCES

1. MATTHEWSCME, DOLLERYCT: Interpretationof ‘33Xelung wash-in and wash-out curves using an analogue cornputer. ClinSci 28:573—590,1965

2. ANDERSEN AM, LADEFOGED : Relationship between hematocrit and solubility of ‘33Xein blood. J Pharmacol Sci54:1684—1685,1965.

3. LAWRENCE JH, LooMIs WF, Tosi@s CA et al: Preliminary observationson the narcoticeffectof xenonwitha reviewof the values for solubilities of gases in water and oils. JPhysiol 105:197-204, 1946

4. Ki@r@'SS:Thetheoryandapplicationsoftheexchangeof inertgas at the lung and tissues. Pharmacol Rev 3:1-41, 1951

5. HARF A, PRATT T, HUGHESJMB: Regional distributionof VA/C in man at rest and with exercise measured withKrypton-81m.JApplPhysiol44:115-123,1978

6. PESETR, HOLLOWAYR, BEEKHUISH, Ctal: Ventilationand perfusion indices measured with xenon-l33 duringspontaneous breathing. Radioact Isot C/in Med Res 9:266—275,1970

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7. PESETR, BEEKHUISH, TAMMELING GJ, et al: A bag-inbox system in regional ventilation studies of the lung withxenon-l33.RadioactIsotClinMedRes 10:335—343,1973

8. PESETR, BEEKHUISH, SLUITER HJ, et al:The measurement of regional alveolar ventilation in liters per minute anddeadspaceventilationusingxenon-133duringspontaneousbreathing.ScandJ RespDisSuppl85:38-45,1974

9. VAALBURGW, STEENHOEKA, PAANSAMJ, et al: Production of 13-N labeled molecular nitrogen for pulmonaryfunction studies. I Lab Comp Radiopharmacol 18:303-308,1981

10. VAN DER MARK THW, PESET R, VAALBURG W, et al:Storage and retrieval of waste ‘33Xe.In: J Appl Radiat Isot28:602-604, 1977

11. SUSSKIND H, ATKINS HL, COHN SH, et al: Whole-bodyretention of radioxenon. J Nucl Med 18:462—471,1977

12. VAN DER MARK THW, PESET R, BEEKHUIS H, et al: Animproved method for the analysis of xenon-i 33 washin andwashout curves. J Nuci Med 21:1029- 1034, 1980

13. WEST JB: Regional differences in gas exchange in the lungoferectman.J ApplPhysiol17:893-898,1962

14. MOULDER PV, ADAMS WE: In Clinical CardiopulmonaryPhysiology, Third Edition, New York, Grune and Stratton,

1969,p 66115. THOMASSON WM, CLARK JW: Analysis of exponential

decay curves:A three-step scheme for computing exponents.Math Biosci 22:179—195,1974

16. WILSoN EM, WILLS EL, RISBERGJ, Ctal: Measurementofregionalbloodflowbythe 1@xenoninhalationmethodwithanon-linecomputer.Comput BiolMed 7:143-157,1977

17. VAN DER MARK THW, PESET R, ROOKMAKER AEC, Ctal: Interpretation of wash-in curves in assessing regionalpulmonaryventilation.BullEuropPhysiopathResp 14:i85P,1978

18. BRUSASCO V, TIAN0 A, ASTENGO R, et al: Identificationmethodsforanalysisofxenon-133washoutcurves:Acriticalcomparative study. In Computers in Critical Care and Pulmonary Medicine 2, Prakash 0, ed. New York, Plenum Press,1982,pp49—53

19. RHODESCG, MACARTHUR CGC, SWINBURNEAJ, et al:Influenceofpulmonaryrecirculationandthechestwalluponmeasurementsof regionalventilation,perfusionand watervolume. BullEurop Physiopath Resp 16:383-394, 1980

20. RONCHETTIR, EWAN PW, JONES I, Ctal: Use of ‘3Nforregional clearance curves compared with ‘33Xe.Bull EuropPhysiopathResp 11:124P-125P,1975

i182 THE JOURNAL OF NUCLEAR MEDICINE

Announcementof Berson-YalowAwardThe Society of Nuclear Medicine invites abstracts for consideration forthe Seventh Annual Berson-YalowAward. @rkwillbe judgedon originalityand contributionto the fields of basic or clinical radioassay.The abstractwill be presentedatthe 32nd Annual Meeting of the Society of Nuclear Medicine in Houston, TX, Sunday, June 2—@dnesday,June 5, 1985,and a suitably engraved plaque will be awarded to the authors by the Education and Research Foundation of the SOCietyof NuclearMedicine.

The abstract should be submitted on the official abstract form wfth a letter requesting consideration for the award.

Deadline for receipt of manuscripts: Thursday, January 10, 1985.

The abstract form may be obtained from the November 1984 Issue of the JNM or by calling or writing:

Society of Nuclear MedicineAttn: Abstracts

475 Park Avenue SouthNew York, NY 10016

(212)889-0717

Featureon ResidencyPositionOpeningsThe January issue ofJNM willprovidea listingof residencypositionsopen in 1985.This feature is sponsored bythe AcademicCouncil as a service to individuals looking for open residency positions and programs with positions to fill. Any residencyprogram wishing to list a 1985 position should contact:

Lori S. CariinSociety of Nuclear Medicine

475 Park Avenue SouthNew York,NY 10016