the distribution of and gas of 133xe - thorax · '33xe. one consisted of flat boxes 20x20x1-4...

Thorax (1963), 18, 316

The distribution of blood and gas within the lungsmeasured by scanning after administration of 133Xe

C. T. DOLLERY AND P. M. S. GILLAM

From the Department of Medicine, Postgraduate Medical School, Hammersmith Hospital, Londont

Many diseases of the lung or the pulmonarycirculation cause regional differences in functionwithin the lungs that may be of both diagnosticand therapeutic importance. The use of the radio-active gases 150 and '33Xe has enabled detailedstudies of regional lung function to be made thatwere not possible with earlier techniques (Dyson,Hugh-Jones, Newbery, Sinclair and West, 1960;Ball, Stewart, Newsham, and Bates, 1962). Thesegases are inhaled or injected into the lungs andtheir distribution is detected by counters arrangedoutside the chest. The precision of the informationgained depends upon the accuracy and uniformityof the counting fields and the number of countersused. Up to the present, counters have been usedeither as pairs arranged in front and behind thechest or singly in a number of different positions.Single counters require less apparatus to surveya number of different areas, but pairs wired inparallel are preferable because they give a moreuniform counting field stretching through the lung.The sensitivity of a single counter falls off rapidlywith distance. As it is often desirable to study thefunction of several areas of lung on the samebreath, a formidable array of electronic equipmentmay be required.The problem is essentially how to display the

distribution of radioactivity within the lung, whichis a large three-dimensional object. Three-dimensional display is not practical at present, buteither a scintillation camera or a scanning methodcould be used to give a two-dimensional picture.The scintillation camera (Anger and Rosenthal,1959) consists of a large crystal or crystals whichact in the same manner as the film in a camerawith a pinhole collimator or similar simplefocusing device. The image on the crystal isdetected by an array of photomultiplier tubes anddisplayed on a cathode ray tube. It has not yetproved possible to apply this method to the lungbut in the future it may have promise. At presentit is more practical to scan the source of radio-activity by moving the counters over it (Brownell,

1959). The shape of the lung, which is very muchlonger in the vertical plane than in any other,means that a single vertical scan is able to detectmost abnormalities of functional importance. Inthis paper we describe the development and useof a profile scanning method which gives moreinformation about the topographical distributionof lung function than can be obtained with quitecomplex arrays of stationary counters.

APPARATUS AND METHODS

The methods used for handling and dispensing radio-active xenon have been published (Dollery, Hugh-Jones, and Matthews, 1962). Pairs of sodium iodidecrystals 1y in. long x lin. thick were used with leadcollimators 6 in. long with an aperture of 1 in. atthe crystal tapering to I in. at the external orifice.Using these collimators with a lung model uniformlyfilled with .33Xe, 87% of counts are contributed froma cylinder 9 cm. in diameter.Each pair of counters was mounted on a rigid metal

frame to ensure accurate alignment. The frame slidvertically on two metal pillars, and movement wascontrolled by a hydraulic jack mounted between thepillars. The hydraulic ram, which was reversible, wasdriven by an electric pump, and the flow of fluid wasregulated by a valve that allowed movement up ordown under power, and a neutral position which re-circulated the fluid to the pump (Fig. 1). Each pairof counters could be moved independently but, forscanning, they were always used coupled together sothat all four moved as a single unit.

Scans were usually made with the counters movingvertically and the patient sitting upright in a chair.However, a special couch could be used for scanswhile the patient lay flat and the counters moved hori-zontally. The motors could move the counters at anyspeed up to 3-8 cm./second.The signals from the counters were amplified and

fed to ratemeters and displayed on a twin pen recorderwith a central marker pen which showed a pulse everyhalf-inch the counters moved. "'Xe emits 80 KeVgamma rays and 30 KeV X rays, and the bias of theamplifiers was adjusted to filter out the 30 KeV peakand with it some of the scattered radiation.

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Blood and gas within the lungs

.ffi-RESOLUTION The resolution of the counters wastested using two different shaped sources filled with'33Xe. One consisted of flat boxes 20 x 20 x 1-4 cm.and the other, glass test tubes 15 x 125 cm. closedwith a rubber bung. Each type was scanned at lowspeed (less than 0-5 cm./sec.) first as a single sourceand then as a pair containing approximately equalamounts of radioactivity. The pairs of sources weregradually separated and the scans repeated. Fromthese data the resolution can be calculated in twoways; first, the width of the scan of a single sourceat half the peak height, and, second, the distanceseparating two sources when it first becomes possibleto distinguish two distinct peaks. Both methods andboth types of source gave a resolution of 3-6 cm.Further studies were made with the tubular type ofsource which was easier to make in large numbers.The pen recorder and ratemeters used previously

for radioactive gas work had an overall time constantof 0-2 second. Modifications were made to a second

_............... ; pair of ratemeters and a special pen recorder wasfitted to decrease the time constant to 01 second. The

FIG.1. Theapparatususedforscanning.Thechairandone two recording systems were compared by scanning apair of counters are shown. The hydraulic ram (arrowed) known distribution of 20 tubes containing 133Xemoves thepair of counters over the chestfrom base to apex. stacked one above the other. When the stacks wereThe electric pump and control valve are at the bottom left. scanned at gradually increasing speeds up to the

maximum of 3-75 cm./sec. there was little differenceSO 0*- SEC. TIME CONSTANT between the recording systems (Fig. 2).

x^--x 0-2 A COMPARISON WITH STATIONARY COUNTERS The sensi-

70 tivity of the scanning system was compared withstationary counters by constructing a stack of sourceswith a sharp dip to zero within it. Three stationary

60 - counter positions were used spaced out over themodel, and the information obtained was comparedwith the known distribution of the counts and withso:.xs N the scan (Fig. 3). When one of the stationary counter

x o^q\xv pairs was directly over the gap it was clearly detected,but when the gap was midway between two pairs they

z 40 -.. \.failed to show it clearly. By contrast the scan, which

Z 4 | | 8 l | L covered the whole of the lung, always revealed the0U I ~~~~~~~~~~~~~~defect.x 1A

/. VALIDITY OF BLOOD FLOW, VENTILATION, AND VOLUME4 . 6; RATIOS DERIVED FROM SCANS Radioactive xenon is

used in lung function studies to compare ventilationc0 . and blood flow in different regions. The counting rate

in each area after a single tidal breath or an intra-venous injection of dissolved xenon gives a measure

0 of the amount entering that region in gas or blood,but to make comparisons it is helpful to know the

-: \s lung volume in each counting field. The lung volumer. . .. . . calibration is made using the counting rate in each0 2 4 6 a 0 12 area after rebreathing a 113Xe mixture with air from

INCHES a closed-circuit spirometer until it has equilibrated.FIG. 2. Scans made at a speed of 3.75 cm./sec. over a If the lung is scanned after an intravenous injectionstack of sources (solid line) with a dip to zero in its lower of dissolved "3Xe and again after rebreathing, the twopart. There is little difference in the shape of the scan curves represent the distribution of blood flow andobtaitned with recording apparatus with an overall time lung volume at each level within the limits of reso-constant of 0-1 sec. and alternative apparatus with a time lution of the system. If the ratios of the heights of theconstant ofO02 sec. two curves are taken, say every I in., a plot can be

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C. T. Dollery and P. M. S. Gillam

Inz

aI-

16

14

.12

1-0 --K

0.8 -

0-6 I

8 10 0 2 4 6 8 10 0 2 4 6 8 10

INCHES ABOVE BOTTOM OF STACK

B. C.

FIG. 3. (Above) The histogram indicates the distributionof radioactivity in the lung models; (below) the continuous-lines show the curves obtained by scanning and the hatchedcolumns readings obtained with stationary counters. Whenone stctionary cou iter is over the gap (B) it gives a clearindication ofit but when the gap is between two counters (C)they fail to detect it. In both instances the scan gives asatisfactory indication of the position of the gap.

80

70-

60-

50

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is

.,

I Il

I

.I

'xx 'x

x

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FIG. 5. The ratio of the known distribution of the sources.in Fig. 4 is shown by the continuous line (0 0) and theratio calculatedfrom the scans by the dotted line (x -- - - x).Over most of the range the agreement is close.

INCHES

FIG. 4. Scans of two stacks of sources chosen to represent the lung after an

injection of 133Xe dissolved in saline and after equilibration on a closed circuit.The histogram shows the distribution of the sources and the continuous line thescan from the counters. For comparison each pair of histograms and scans havebeen scaled to an equal area.

I-

izn

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A.

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made of the flow per unit lung volume up the lung.A similar method is used with the scans after a tidalbreath to make ventilation/volume and ventilation/blood flow comparisons. To test the validity of usingthe scans in this way two stacks of sources were made,one to simulate blood flow and the other volumedistribution in the upright normal lung (Fig. 4). Theratio of 'flow/volume' was derived from the two scansand also from the known ratios of the distributionof radioactivity in the two stacks of sources (Fig. 5).The two agree closely except at the extremes wherethe counters were at the limits of the stacks ofsources.

CLINICAL APPLICATIONS

Clinical lung scans are made with the patientssitting upright in a chair and with the countersat rest over the lowermost part of the chest. Theblood flow measurement is made after injectionof about 1 millicurie of 133Xe dissolved in salinethrough a fine (PE 60) polythene catheter passedfrom a needle in an arm vein into the superiorvena cava. Five seconds after injection the patientis asked to start breathing slowly in and then tohold his breath. The scan is made 10 seconds afterthe injection is complete and it takes about sixseconds. A further scan is made at 30 secondsafter the end of the breath-holding period todetermine the rapidity of wash-out of the injected133Xe from the lungs. The ventilation measure-ment is made during breath holding after a singletidal breath in of 133Xe in a concentration of1 to 2 millicuries per litre from a spirometer. Ascan is made at 30 seconds after the end of breathholding to measure the wash-out.

Rebreathing studies are made for two purposes;to calibrate the scans for the lung volume in thefield at each level and to examine the wash-inand wash-out of poorly ventilated areas. Thepatient breathes "33Xe at a concentration of 1 to2 millicuries per litre from a closed-circuit spiro-meter, and scans are made during breathing at30 seconds after starting and then at every minuteafter starting. If ventilation is normal the lungsand spirometer reach equilibrium after about oneand a half minutes but if there are poorlyventilated areas, as in bullous emphysema, it maybe impossible to reach equilibrium in a fewminutes. In a patient with poorly ventilated areasrebreathing is continued for four to six minutesand at the end a scan is made with the patientbreath holding in inspiration. Further scans aremade during normal air breathing, at minuteintervals, as the 133Xe is washed out of the lungs.At the end of the procedure the counters are setopposite the second rib and a note is made of the

height above the bottom of the scan. This enablesfunctional abnormalities to be related to structuralchanges shown on the chest radiograph.With the amounts of radioactivity used in these

studies and the counting apparatus described, thecounting rate is about 300 counts per second afterthe injection and the tidal breath and 1,000 c.p.s.after equilibration. The radiation dose does notexceed 300 miflirads to the lungs in a patient withpoor ventilation in some areas, and if ventilationis normal the dose is slightly less (Cyclotron UnitTechnical Memo No. 84).The scan curves can be analysed in several ways.

The simplest method is to take the ratios ofdeflection at standard points on each scan to mapout the distribution of perfusion/volume, ventila-tion /volume or ventilation / perfusion. By assumingthat the whole of both lungs are scanned the totalarea under each scan can be taken as 100% ofperfusion, ventilation, and volume respectively,and a plot can be made in terms of the percentageof the total of each appearing in a given amountof the lung. The wash-in and wash-out scans canbe analysed either by taking the deflections atdifferent times to draw a curve of the change inactivity with time at different positions or, moresimply, to trace and superimpose curves togain an approximate idea of the ventilationcharacteristics of different areas.Some examples of the applications of the

method and the different methods of analysisfollow.

DISTRIBUTION OF FUNCTION IN THE NORMAL LUNG

The scans in Fig. 6 were made from a 27-year-olddoctor who had been sitting at rest in a chairfor 10 minutes. The striking feature is that thepeak of the scan following injection of "33Xe('perfusion') is much lower down the chest thaneither the one taken after a tidal breath ('ventila-tion') or after equilibration on a closed circuit('volume'). The ratios of perfusion/volume,ventilation /volume, and ventilation / perfusion areshown in Figure 7. To facilitate comparison eachscan has been scaled to the same area so thatin each case the ratio for the whole lung is unity.The blood flow per unit of lung volume is fivetimes higher at the base of the lung than at theapex but the ventilation is much more evenlydistributed. In consequence the ventilation/perfusion ratio is nearly five times higher at theapex than at the base. The distribution of functionis similar to that found by West and Dollery (1960)using CO02. The scan allows a topographical

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X, PE RFUSION VENTILATION VOLUME -

N.,

O UNT Aq; T r) 'i , Af;tft; ''Y'j

.3.Nh -

..

i33Xe SC ANIS NOR!MA 5 fjSJ -1 E -.

FIG. 6. Scans in a normal subject after a 133Xe injection (perfusion), a tidal breathof 133Xe (ventilation), and after rebreathing the isotope on a closed circuit untilequilibrated (volume). The centre marker indicates displacement every half inchfrom base (B) to apex (A). Note the peak is much lower down the chest after theinjection than after either the tidal breath or equilibration.

PERFUSION/VOLUME2422201[81 61-42

1.00806

,a 04[02 [

10 0

VENTILATION/VOLUME

I 5 10

INCHES ABOVE LUNG BASE

FIG. 7. Distribution of perfusion/volume, ventilation/volume, and ventilation/perfusioncalculatedfrom the scans ofa normal subject in Fig. 6. The perfusion per unit volume is fiveto six times higher at the base than at the apex. The ventilation per unit volume is only slightlyhigher at the base than at the apex; in consequence the ventilation/perfusion ratio is four tofive times higher at the apex than at the base (*.e left lung; x - x right lung).

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FIG. 8. Chest radiograph of a58-year-old man with breathless-ness on slight exertion. Thediaphragms are low buit there is noregional abnormality in the lungfields.

FIG. 9. A sketch of the chestradiograph in Fig. 8 with theventilation and perfusion dividedas apercentage oftotal in six hori-zontal slices over each lung. Theventilation/perfusion ratio is sixtimes higher in the uppermost slicethan in the lowest.

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0

z

FIG. 10. Scans of ventilation (o-o) :and perfusion (x - - x) redrawn to equoalIareas in the patient whose radiograph is 2Fig. 8. The perfusion is evenly distributed Wbut the ventilation is preponderantly 1

distributed to the upper zones. The ,ventilation/perfusion ratio (a- *) is 10 atimes higher in the upper part of the left rlung than in the lower.

z

z0

INCHES ABOVE LUNG BASE

FIG. 11. Chest radiograph ofa woman of 55 showing bilateral basal bullae, largeron the left than the right.

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LEFT S_ -:

LU NG

Counting

LUNG 4%.

Rt

1 2

INC

FIG. 13. The scawscale. Where the stthe wash-out is fctogether the wash-idifference in initial

B -.-.--

'K-

-f \--

-z

t = 45 secs. t = 3mins. 4 5 secs. t=13mins. 45secs,

FIG. 12. Scans made sequentially during air breathing after six minutes rebreathing133Xe by thepatient whose radiograph is Fig. 1 1. More radioactivity had entered theapical regions (A) than the base (B) at the end of the period ofrebreathing, labelledt=O. During air breathing the wash-out was much faster at the apex so that after131 minutes more was left at the base despite its initially low activity.

,s,, x x assessment of function in a single study whereasHING XG. methods using stationary counters usually require

After / pooling of several studies to produce a similarsect BreaithingAil, /\ detailed profile of the distribution of blood flowx g <, \ and ventilation.

x / ^ o \EMPHYSEMA AND BRONCHITIS The first patient, aman of 58, had a 15-year history of bronchitisand had become increasingly breathless over twoyears. He was able to walk only a few paces beforehe became dyspnoeic. His chest radiograph

_N showed only minor bullous changes in the mid-zones with flat and low diaphragms. The scans

3 4 5 6 7 8 9 io revealed that 74% of the total ventilation wasgoing to the upper half of the lungs which werereceiving 53% of the blood flow. The lower half

&,¢iH \ of the chest received only 27% of the ventilationbut had 46% of the blood flow (Fig. 9). Theventilation and perfusion scans on which these

x results are based are shown drawn to equal areasin Figure 10. By displaying the chest radiographand function divided up into 2-in. thick slices oflung on the same scale it is possible to appreciatethe distribution of function in relation toanatomical features on the radiograph (Fig. 8).Another patient, a woman aged 55 years, was

disabled by breathlessness on slight exertion. Herradiograph showed bilateral bullae at the lung

3 4 5 6 7 8 9 10 bases (Fig. 1). The ventilation and perfusion scans,HES ABQVE THE LUNG BASE both showed little function in the bullous zone,is of Fig. 12 replotted on to a common and ventilation and perfusion were reasonably wellcan lines are wide apart, as at the apex, balanced in contrast to the previous patient.aster whereas where they are crowded During rebreathing, little "33Xe entered the bullaeout is very slow (after allowing for the and what did was very slowly removed duringI deflection). air breathing. By replotting the traces during wash-

to

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out on to a common graph, it is possible to buildup a contour map of ventilatory function (Figs.12 and 13). As some '33Xe is taken up into theblood during breathing and is slowly returned tothe lungs from the tissues, the wash-in and wash-out plots are not purely a measure of alveolarventilation. However, for clinical purposes thedifferences between poorly ventilated and morenormal areas are usually so great as to make thisfactor relatively unimportant.

MITRAL STENOSIS Changes in pulmonary vascularpressures cause alterations in the normal distribu-tion of blood flow within the lungs, and one ofthe most remarkable changes that takes place isthat of severe mitral stenosis. In this condition theblood flow is reduced so that in severe cases it maybe much less than in the upper zones of the lungs.There is no corresponding change in ventilation(Dollery and West, 1960). The patient whosepulmonary angiogram is shown in Fig. 14 was awoman aged 56 years who had extremely severemitral stenosis with a resting pulmonary arterypressure of 90/27 mm. Hg. The scans for the

FIG. 14. Pulmonary angiogram of the right lung of a

patient with severe mitral stenosis. The blood vessels areattenuated at the lung base.

right lung are shown alongside the arteriogramto show that the blood flow per unit volume wasmore than four times higher at the apex than atthe base whereas ventilation was evenly distributedthroughout (Fig. 15).

10 10

Wrz

0 1 2 0 1 2

FLOW/VOLUME VENTILATION / VOLUMEFIG. 15. The distribution ofbloodflow and ventilation perunit volume in the right lung of the patient with mitralstenosis whose pulmonary angiogram is Figure 14. Thevertical scale shows the height above the lung base and thehorizontal one is an arbitrary ratio scaled to unity for thewhole lung. The blood flow per unit volume is four timeshigher in the upper part of the lung while ventilation isevenly distributed.

DISCUSSION

The objective of studies of regional lung functionis to map out the distribution of ventilation andblood flow within the lungs so as to produce afunctional equivalent of the chest radiograph.Radioactive gas studies have made a substantialcontribution towards realizing this objectivebecause of the ease with which they can be usedand the small areas that can be studied.The scanning method has some substantial

advantages over the use of a complex array ofstationary counters to examine many areas on asingle breath or injection. First it gives acontinuous picture of the distribution of functionfrom top to bottom of the lung and thus reducesthe possibility of missing a lesion because it didnot fall within the field of a counter. Anotherimportant advantage is the economy of apparatusthat it makes possible. Two pairs of scintillationcounters with their associated amplifiers, rate-

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meters, and recorders supplemented by £250 ofhydraulic equipment will do more than can bedone with six or eight pairs of stationary counterswhich, with their ancillary equipment, would costseveral thousand pounds more.The scanning method is suitable for recording

distribution following intravenous injection and atidal breath and is suitable for wash-in and wash-out studies if the scans are repeated frequently.There are several possible sources of error. As

the ratios are taken from scans done at differenttimes it is important to ensure, as far as possible,that the patient is in the same position and at thesame lung volume for each of them. The chairused is designed to prevent changes in postureby use of a head and backrest but close attentionto position is essential. The easiest way to reachthe same lung volume in disabled patients is toask them to breathe in as deeply as they can foreach scan.For the perfusion measurement it is important

that the patient should not close the glottis anddo Valsalva's manoeuvre while the 133Xe isarriving in the lung. This difficulty is overcomeby asking him to breathe in slowly, and once theradioactivity has been evolved into the alveolargas it does not matter if the patient does strainagainst a closed glottis during breath holding.

In patients with bullous emphysema some areasof lung may be very poorly ventilated andequilibration only very slowly reached duringrebreathing. Rebreathing cannot be continued formore than six minutes because of radiation dosage,and this may not be long enough to reachequilibrium. Under these circumstances the'volume' scan will be too small, and ventilationand perfusion related to this volume will be over-estimated. Results of ventilation and perfusionscans in such patients are best expressed as apercentage of the total for the whole lung goingto particular areas. Volume figures derived fromradiographs would be an alternative method if itwere important to relate ventilation and perfusionto volume.The scanning method could be used in any body

position although our apparatus has only beenused with the chest upright or lying flat. Mostpatients have to be studied with the chest uprightbecause they are too breathless when lying down.The method has proved useful in evaluating

patients who have regional abnormalities offunction, and it is a very easy test for the patientto perform. The applications are similar to those

of the earlier 133Xe procedure (Ball et al., 1962;Dollery et al., 1962) and include a wide varietyof diseases of the lungs and the pulmonary circula-tion. As the scans give a more complete pictureof function, judgments about the proportion ofblood flow and ventilation entering different areascan be made with greater certainty.

SUMMARY

A method has been devised of using pairs ofcollimated crystal scintillation counters, driven byhydraulic rams, to scan the lungs after intravenousinjection or inhalation of 133Xe.

Tests with a lung model show that the resolutio5.of the counters for point sources is 3'6 cm. andthat when the counters are propelled at 3-8 cm./sec. an overall time constant of the recordingapparatus of 0-2 sec. is adequate.The scan records the profile of distribution of

radioactivity in the vertical plane, and tests withknown sources show good agreement between thereal and calculated distributions.

In clinical studies the scans can be used to mapout the distribution of blood flow and ventilationand to record the rate of wash-in and wash-outduring rebreathing.The method gives more information with less

apparatus than is required for a complex arrayof stationary counters.

We thank Mr. G. Forse for skilled technical assist-ance. We are grateful to Dr. P. Hugh-Jones for hissupport and to members of the staff of the M.R.C.Cyclotron Unit, particularly Mr. D. D. Vonberg andDr. C. M. E. Matthews, for advice and facilities.

REFERENCES

Anger, H. O., and Rosenthal, D. J. (1959). In Medical RadioisotopeScanning, p. 59. International Atomic Energy Agency, Vienna.(Proceedings of a seminar organized by I.A.E.A. and W.H.O.).

Ball, W. C., Stewart, P. B., Newsham, L. G. S., and Bates, D. V.(1962). Regional pulmonary function studied with xenon. J. clin.Invest, 41, 519.

Brownell, G. L. (1959). In Medical Radioisotope Scanning, p. 1. Inter-national Atomic Energy Agency, Vienna. (Proceedings of aseminar organized by I.A.E.A. and W.H.O.).

Dollery, C. T., Hugh-Jones, P., and Matthews, C. M. E. (1962). Useof radioactive xenon for studies of regional lung function. Acomparison with oxygen-15. Brit. med. J., 2, 1006.

- and West, J. B. (1960). Regional uptake of radioactive oxygen,carbon monoxide and carbon dioxide in the lungs ofpatients withmitral stenosis. Circulat. Res., 8, 765.

Dyson, N. A., Hugh-Jones, P., Newbery, G. R., Sinclair, J. D., andWest, J. B. (1960). Studies of regional lung function using radio-active oxygen. Brit. med. J., 1, 231.

West, J. B., and Dollery, C. T. (1960). Distribution of blood flow andventilation-perfusion ratio in the lung, measured with radioactiveCO2. J. appl. Physiol., 15, 405.

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the distribution of and gas of 133xe - thorax · '33xe. one consisted of flat boxes 20x20x1-4...

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