Fluid Dynamics of Gas Exchange in High-Frequency Oscillatory

Ventilation: In Vitro Investigations in Idealized and Anatomically

Realistic Airway Bifurcation Models

KEVIN B. HERATY,1,2 JOHN G. LAFFEY,3,4 and NATHAN J. QUINLAN1,2

1Department of Mechanical and Biomedical Engineering, National University of Ireland Galway, Galway, Ireland; 2NationalCentre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland; 3Lung Biology Group,National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland; and 4Department

of Anaesthesia, Galway University Hospitals, Galway, Ireland

(Received 1 November 2007; accepted 25 August 2008; published online 11 September 2008)

Abstract—The objective of this work is to develop under-standing of the local fluid dynamic mechanisms that under-pin gas exchange in high-frequency oscillatory ventilation(HFOV). The flow field during HFOV was investigatedexperimentally using particle image velocimetry in idealizedand realistic models of a single bifurcation. Results show thatinspiratory and expiratory fluid streams coexist in the airwayat flow reversal, and mixing between them is enhanced bysecondary flow and by vortices associated with shear layers.Unsteady flow separation and recirculation occurs in bothgeometries. The magnitude of secondary flow is greater in therealistic model than in the idealized model, and the structureof secondary flow is quite different. However, other flowstructures are qualitatively similar.

Keywords—Respiratory flow, Mechanical ventilation, Lung,

Particle image velocimetry.

INTRODUCTION

The aim of this study is to develop an improvedunderstanding of the fluid dynamics of high-frequencyoscillatory ventilation (HFOV).HFOV is a shallow, fastmode ofmechanical ventilation which can avoid the riskof lung injury associated with cyclic opening and closingof alveolar units in conventional ventilation.16 HFOVhas been successfully applied to neonates since 1981,18

and more recently to adolescents20 and adults.1,6,19

HFOV results in better pulmonary outcomes thanconventional mechanical ventilation for very low birthweight infants suffering with respiratory distress syn-drome.27 In adults suffering from acute respiratorydistress syndrome (ARDS), Derdak et al.6 showed that

HFOV is at least as effective as conventional ventilationstrategy. However, HFOV remains a relatively new andincompletely understood mode of ventilation. An im-proved fundamental understanding of gas exchange inHFOV is essential in order to harness its potential toimprove outcome in patients with ARDS.

Breathing frequencies from 60 to 2400 breaths perminute with tidal volumes of 35–150 mL have beenused in HFOV,16 whereas in normal breathing, thetypical rate is 12 breaths per minute with a tidal vol-ume of 500 mL. The anatomical dead space (the vol-ume of the conducting airways) is approximately150 mL. In normal breathing, therefore, 350 mL of theinspired 500 mL is transported to the alveoli for gasexchange. In HFOV, however, since the tidal volume isusually less than the anatomical dead space, gas ex-change cannot be explained in terms of simple advec-tive bulk transport to the alveoli.

More detailed knowledge of HFOV fluid dynamicsis essential in order to develop HFOV systems andstrategies that optimize gas exchange, and potentiallyimprove outcome from acute lung injury (ALI) andARDS. It is apparent from previous research thatTaylor dispersion and secondary flow, particularly atflow reversal, have a significant impact on dispersion,and hence on the effectiveness of gas exchange inHFOV. Collectively, these can be classified as con-vective phenomena which act locally (within an indi-vidual bifurcation) to enhance axial mixing (that is,mixing between O2-rich gas in upper regions of theairway and CO2-rich gas in lower regions). The pur-pose of this study is to develop a better understandingof these fluid dynamic mechanisms and their interac-tions in HFOV.

This paper describes an investigation of the fluiddynamics of HFOV at the level of a single airway

Address correspondence to Nathan J. Quinlan, Department of

Mechanical and Biomedical Engineering, National University of

Ireland Galway, Galway, Ireland. Electronic mail: nathan.quinlan@

nuigalway.ie

Annals of Biomedical Engineering, Vol. 36, No. 11, November 2008 (� 2008) pp. 1856–1869

DOI: 10.1007/s10439-008-9557-1

0090-6964/08/1100-1856/0 � 2008 Biomedical Engineering Society

1856

bifurcation. The goal is to identify and understandlocalized fluid dynamic mechanisms which augmentbulk transport by promoting mixing in the axialdirection. Two-component particle image velocimetry(PIV) and stereoscopic particle image velocimetry(SPIV) were used to measure the flow field quantita-tively in in vitro models of a single bifurcation at flowconditions representative of HFOV in the upper air-way. Models were scaled up to enhance the effectivespatial and temporal resolution of the measurements.To identify and differentiate flow phenomena with thegreatest possible clarity, experiments were carried outfirst in an idealized geometry. Measurements were alsomade in a realistic geometry, in order to investigate theeffects of nonideal geometry on flow structures.

METHODS

The idealized and realistic geometry models areshown in Fig. 1. The idealized model consists of asingle symmetric bifurcation with the geometry definedby Comer et al.,5 based on the morphological work ofWeibel.34 The flow divider is rounded with a radius of0.1 times the diameter of the daughter branch. Therealistic model is based on images of a third-generationairway bifurcation from the inferior lobar bronchus ofthe left lung. The images were acquired from thefemale data set of the Visible Human Project�.2 Ima-ges were manipulated with image processing and sur-face modeling software (Mimics� and Rhinoceros�,respectively) to generate a three-dimensional geometricdescription of a third-generation lung bifurcation. Theparent and daughter branches have noncircular crosssections, and their centerlines are not coplanar andhave slight three-dimensional curvature. The right andleft daughter branches divide at 24� and 20� to the

parent branch centerline, respectively. Extension sec-tions have been added to all inflow and outflow portsof the realistic geometry. In the extension sections,there is a smooth transition from the realistic ana-tomical cross section of the airway branch to a circularcross section, allowing circular-section tubes to becoupled to the physical model for experimental testing.Using the surface modeling software, continuity wasenforced across surface boundaries to avoid any steps,sharp edges, or curvature discontinuities.

To improve the spatial and temporal resolution ofthe experiment, the geometry was scaled up by a factorof 5.6. Thus, the parent branch diameter scaled from5.3 mm in the third-generation lung airway to 30 mmin the experimental model. To ensure validity of thescaling by complete dynamic similarity, the Reynoldsnumber Re (dimensionless velocity) and Womersleynumber a (dimensionless frequency) must be preservedin the scale models. This was enforced with a 59/41%(by volume) glycerol/water mixture as the workingfluid along with reductions in flow velocity and oscil-lation frequency. The frequency reduction enhancesthe effective temporal resolution of the experiment by afactor of 56.2. The composition of the glycerol–watermixture is also influenced by optical considerations, asdiscussed below.

Tests were carried out for two Reynolds numbers,Re = 740 and 1480, and two Womersley numbers,a = 4.3 and 7.0. The Womersley number a = D/2 (2pf/m)1/2 characterizes the unsteadiness of oscillatory flows,where D = 2a is the airway diameter, f is the frequencyof oscillation of the flow, and m is the kinematic vis-cosity. For a � 1 the flow is quasi-steady, but for higha unsteady effects are important. In terms of clinicalparameters, frequency is proportional to a2 in a givengeometry. Throughout this article, the Reynoldsnumber Re = UD/m is based on the mean velocity in

Idealised model Realistic model

daughterbranches

parent branch

left branchright branch

parent branch

PIV measurementplanes PIV measurement

plane

SPIV measurementplanes

Point A

daughterbranches

me

Point A

Y

Z

X

Line A

Y

Z

X

ZX

Y

FIGURE 1. Geometrically accurate sectional views of the idealized and realistic experimental models, showing PIV and SPIVmeasurement locations.

Fluid Dynamics of Gas Exchange in HFOV 1857

the parent branch at peak inspiration, denoted by U.At the level of the third-generation airway, Re = 1480and a = 4.3 corresponds to a tidal volume of 47 mLthrough the trachea at 377 breaths/min, representativeof a HFOV condition. The test cases may also becharacterized in terms of a dimensionless flow ampli-tude, L/a, where L is the mean displacement of a fluidparticle over one cycle, based on bulk transport, and ais the tube radius. The three dimensionless parametersare not independent, as Re = a2L/a. The four testcases in this study are summarized in Table 1. All fourtest conditions fall within the flow regime dominatedby the effects of convective acceleration, as defined byJan et al.14

Rigid experimental models were made in SylgardTM

184 (Dow Corning�) transparent silicone by a lost core

technique described by Kelly et al.15 The geometry ofthe experimental models was validated by comparingcomputed topography (CT) scans of the siliconemodels to the original CAD geometry models. Mea-surements were made at 118 cross sections in the ide-alized and realistic models, respectively, and it wasfound that the average cross-sectional area in theexperimental models was 3% greater than in the ori-ginal CAD geometry models.

The flow apparatus, shown in Fig. 2, supplied acontrollable time-varying flow rate through theexperimental model, while allowing unobstructedoptical access for both two-component PIV and SPIV.A sinusoidal flow rate was applied to the experimentalmodels by a custom-built computer-controlled pistonpump, with a maximum stroke length of 1 m and amaximum stroke volume of 15.4 L. The pump wasdriven by a position-controlled stepper motor (SanyoDenki Co. Ltd., 103-H8223-6540), which was con-trolled by a computer with a custom-designed Lab-VIEWTM 7 program.

Straight tubes were attached at all inflow and out-flow ports of the experimental models to minimizeentrance and exit effects. Gerrard and Hughes10 foundexperimentally that oscillatory flow is fully developed

TABLE 1. Summary of test conditions.

Test case Re a L/a

1 740 4.3 40

2 740 7 15

3 1480 4.3 80

4 1480 7 30

stepper motor

experimentalmodel

air-trap

motor drive unitand power supply

motion controlcomputer

3 m

pistoncylinder

ball screwtraverse

fill pump

reservoir

flow disrupterball valve gate valve Flow straightener

FIGURE 2. Schematic diagram of the experimental flow apparatus.

HERATY et al.1858

at a distance of (0.08)a2u0/m from the tube entrance,where a is the tube radius, u0 is the mean velocity basedon peak flow, and m is the kinematic viscosity. Theentrance tubes used in this study were 30% longer thanthe required entrance length.

A flow disrupter and a flow straightener wereattached to each straight tube section as shown inFig. 2, at the opposite end from the bifurcation model,to condition the intake flow from the pump or reser-voir. Each flow disrupter consists of a short tube full ofglass spheres. Their function is to provide a uniformaxial velocity profile. Each flow straightener consistsof a bundle of parallel small-bore thin-walled tubes,intended to remove any radial and swirl velocitycomponents. Flow rates through the daughter bran-ches of the idealized geometry were measured in steadyexpiratory flow using PIV, and were matched to within1% by adjusting the gate valves shown in Fig. 2.

The refractive index of the working fluid and theSylgard 184 silicone was measured at 20 �C using anAbbe refractometer with sodium D light, and wasfound to be 1.411 for both materials. Chrome-coatedhollow glass tracer particles of diameter 10 lm wereadded to the fluid mixture.

Instantaneous full field measurements were madeusing two-component PIV and three-componentSPIV at different locations. The plane of measurementwas illuminated with Nd:YAG lasers (New WaveResearchTM, Gemini PIV Laser). Images were cap-tured using a 1000 9 1016 pixel CCD camera (TSI,PIVCAMTM 10–30) with 8-bit digitization.

Measurement was triggered at the start of inspira-tion for each cycle by an electronic switch mounted onthe frame of the piston pump. All PIV images wereprocessed using 32 9 32 pixel interrogation windows,and each interrogation window overlapped neighbor-ing interrogation windows by 50%. A 32 9 32 pixelinterrogation window corresponds to a 1.7 9 1.7 mm2

region of the measurement plane. SPIV images wereprocessed using 16 9 16 pixel interrogation windowswith 50% overlap. Each 16 9 16 pixel interrogationwindow measured 1.5 9 1.5 mm2. The velocity fieldwas sampled at a rate of 7.5 Hz for tests at a = 4.3 andat 15 Hz for a = 7.0. According to the Nyquist theo-rem, this would allow measurement of fluctuations upto 3.25 and 7.5 Hz, respectively, or up to 29 and 26times the base cycle frequency. Particle images wereprocessed by two-frame cross-correlation using Insight3GTM 8.0.5 software.13 Using the data of Raffelet al.,25 measurement uncertainty for this PIV config-uration was estimated as 0.007 m/s, or 1.6% of thepeak flow velocity.

The two-component PIV measurements were cali-brated using dimensions measured in CT images of theexperimental models. The SPIV measurements were

calibrated by placing a three-dimensional calibrationtarget in the fluid-filled model at the measurementlocation. A correction procedure was implemented forall SPIV measurements using Insight 3GTM 8.0.5software13 to reduce error due to misalignment be-tween the calibration target and the measurementplane.

The locations of the measurement regions for theidealized and realistic geometries are illustrated inFig. 1. In both experimental models, all two-compo-nent PIV measurements were acquired on a planepassing through the centers of the three inlet/outletports. This is defined as the xz plane in the Cartesiancoordinate system shown in Fig. 1. This coordinatesystem is used throughout this article to indicate therelative orientation of measurement planes. For theidealized geometry, the z-axis corresponds exactly withthe centerline of the parent branch. The outlines of theidealized and realistic models, shown in Fig. 1, are theintersections of these xz measurement planes with thesilicone experimental models. Seven overlapping mea-surement regions, measuring 58 mm 9 58 mm, wereused in each geometry model to map the velocity fieldon the xz plane with two-component PIV. However,only those field measurements near the flow dividerwill be shown here. SPIV measurements were acquiredon a number of xy planes (i.e., transverse sections)through the parent branch of each model, and resultswill be presented here for the measurement planenearest the flow divider. PIV and SPIV measurementswere captured at similar times, allowing PIV and SPIVresults to be considered in association. All results arenondimensionalized with respect to U, the meanvelocity in the parent branch at peak inspiration.

The velocity fields presented are phase-averagedover 6–10 cycles. The cycle-to-cycle variation in themean velocity on line A at peak flow was 2% of theaverage (line A is a line parallel to the x axis, passingthrough the centerline of the parent branch, as shownin Fig. 1).

RESULTS

Detailed velocity measurements are presented inFigs. 3–6 for L/a = 15, Re = 740, and a = 7.0. Qual-itatively similar flow structures were observed for alltest cases, and these results may be considered repre-sentative. Figures 3 and 4 illustrate the phase-averagedflow field in the idealized and realistic bifurcationgeometries, at dimensionless times s = 0.057, 0.115,0.452, and 0.623. s is dimensionless time t/T, wheret = 0 is at the start of inspiration, and T is the period.In the two-component PIV visualizations (Fig. 3),vectors represent the magnitude and direction of

Fluid Dynamics of Gas Exchange in HFOV 1859

velocity. In the SPIV measurements (Fig. 4), the colormap indicates the axial component (z-direction) ofvelocity (i.e., the component parallel to the nominalcenterline of the parent branch) and the vectors indi-cate the magnitude and direction of the in-plane sec-ondary flow.

Figure 3 illustrates the two-component velocity fieldmeasurements in the idealized and realistic bifurcationmodels. In both models at the beginning of inspiration(s = 0.057), the fluid at the walls reverses and begins toflow in the inspiration direction, while the faster-

moving flow in the core of the airway continues to flowin the expiration direction, as in classical Womersleyflow.35 As a region of inspiratory flow develops nearthe walls, the shear layer between the opposing flowsmoves outwards from the wall. Figure 4 illustrates thethree-component SPIV measurements. The shear lay-ers are also evident in the stereoscopic measurement onthe parent branch cross section. Throughout Figs. 3and 4, the location of the shear layer is indicatedapproximately by the contour of zero z velocity. Asecondary flow consisting of four longitudinal vortices

FIGURE 3. Nondimensionalized two-component PIV measurements in the idealized and realistic bifurcation models at L/a 5 15,Re 5 740, and a 5 7.0. Dotted lines represent contours of zero velocity.

HERATY et al.1860

is present in the parent branch of the idealized modelduring expiration, as illustrated in the stereoscopicmeasurement (Fig. 4). These vortices are associatedwith the curvature of the daughter branches as theymerge into the parent branch. Similar Dean-type vor-tical structures have been observed by other authors8,14

during the expiration phase in idealized bifurcationmodels. In the stereoscopic view of the realistic model(Fig. 4) a single axial vortex is observed at the low y

side of the cross section, and is superimposed on theinspiratory and expiratory fluid streams.

At s = 0.115 in the idealized geometry PIV mea-surement, the shear layers are observed closer to thecore of the parent and daughter branches. The sec-ondary flow vortical structures, observed at s = 0.057,are still present in the parent branch, but the vorticeshave moved closer to the core of the branch. It isapparent from the stereoscopic measurement that these

FIGURE 4. Nondimensionalized SPIV measurements in the idealized and realistic bifurcation models at L/a 5 15, Re 5 740, anda 5 7.0. Dotted lines are contours of zero axial velocity.

Fluid Dynamics of Gas Exchange in HFOV 1861

vortices span the counterflowing inspiratory andexpiratory streams. The stereoscopic measurement(Fig. 4) also indicates that the axial flow in the crosssection is not axisymmetric at this location in theparent branch. At s = 0.115, inspiratory axial flow isobserved first at the high and low x walls, but in themajority of the cross section, flow is in the negative z(expiratory) direction.

In the realistic model at s = 0.115, the shear layersare still present in the parent and daughter branches,but their structure has changed from that observed ats = 0.057. There is now a single shear layer in both theparent and left daughter branches, while a separateshear layer is observed in the right daughter branch.The corresponding stereoscopic measurement indicatesthat the shear layer in the parent branch is closer to thecore of the branch than was observed at s = 0.057. Anaxial vortex structure is still present.

At peak inspiration in the idealized model ats = 0.250, all flow is in the direction of inspiration,and the structure is essentially quasi-steady. (Thequasi-steady flow structure has been described in pre-vious studies17 and is not illustrated here.) Ats = 0.452, when the flow is decelerating from peakinspiration, flow separates upstream of the bifurcation,and recirculation regions are created. However, themajority of the flow in the daughter branch is still in

the inspiration direction. At s = 0.623, shortly afterthe mean flow reverses from inspiration to expiration,the slower-moving fluid at the walls of the parentbranch and at the outer walls of the daughter branchesis the first to change to the expiration direction. Thefaster-moving fluid in the core of the parent branchand at the inside walls of the daughter branches is stillmoving in the inspiration direction. Shear layers existbetween these opposing fluid streams. The stereoscopicmeasurement in the parent branch (Fig. 4) confirmsthat the two shear layers visible in the two-componentPIV measurement (Fig. 3) are part of a single cylin-drical shear layer structure. The structure of the shearlayers in both models near flow reversal is visualized inFig. 5 using instantaneous streamlines, which werecomputed using TecplotTM 10 and initiated at pointsdistributed throughout the bifurcation. In bothgeometry models, vortical structures are observedwithin the shear layers around both flow reversal times.

In the realistic model as the cycle reaches peakinspiration at s = 0.25, the flow structure resemblesquasi-steady flow. A small recirculation region formson the inside wall of the bifurcation in the rightbranch. This recirculation region is caused by the localcurvature at the flow divider, as shown in Fig. 3 ats = 0.452. As the flow changes direction at the start ofthe expiration phase at s = 0.623, the slower moving

Time

Flo

wra

te

τ = 0.075τ = 0.604

Y

Z

X Y

Z

X

τ = 0.604Y

Z

X

τ = 0.075Y

Z

X

FIGURE 5. Instantaneous streamlines at both flow reversals in the idealized and realistic models.

HERATY et al.1862

flow along the outer walls changes direction first,whereas the flow along the core of the parent anddaughter branches is still moving in the inspirationdirection. In the parent branch the shear layer is visiblebetween the last of the inspiratory flow at the core ofthe branch and the expiratory flow at the perimeter.

The temporal variation of the mean magnitude ofaxial and transverse velocity at various section lines inthe xz measurement plane is shown for both models inFig. 6. The magnitude of transverse velocity is anindication of the level of secondary flow. At section1W (in the parent branch of the idealized geometry),

Section 1W

Section 2W

Section 3W

Section 4WY

Z

X

Section 4R

Section 1R

Section 2R

Section 3R

Y

Z

X

00

0.25

0.5

0.75

1.0

1.25

0.25

0.5

0.75

1.0

1.25

0

0.25

0.5

0.75

1.0

1.25

00

0.25

0.5

0.75

1

1.25

0 1/2 10

0.25

0.5

0.75

1.0

1.25 Section 1W Axial velocityTransverse velocity

Dim

ensi

onle

ssve

loci

ty Section 1R

00

0.25

0.5

0.75

1.0

1.25 Section 2R

0

0

0.25

0.5

0.75

1.0

1.25 Section 3R

Section 4R

Section 2W

Dim

ensi

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ssve

loci

ty

Section 4W

Section 3W

Dim

ensi

onle

ssve

loci

tyD

imen

sion

less

velo

city

00

0.25

0.5

0.75

1.0

1.25

1/2 1

1/2 1

00

1/2 1

τ

1/2 1

1/2 1

1/2 1

0 1/2 1τ

FIGURE 6. Magnitude of nondimensionalized axial and transverse velocity averaged over various transverse lines (indicated atthe top of the figure) in the measurement plane in the parent and daughter branches of (a) idealized and (b) realistic models.

Fluid Dynamics of Gas Exchange in HFOV 1863

axial velocity dominates for most of the HFOV cycle,except at times of flow reversal. The magnitude oftransverse flow increases just after peak expiration, butremains small compared to the axial velocity. Closer tothe bifurcation, at section 2W, the transverse velocity is2% of the axial velocity at inspiration, and increases to10% during the expiration phase. In the left daughterbranch, at section 3W and 4W, the peak transversevelocity occurs during the inspiration phase. Trans-verse velocity is higher than axial velocity during flowreversal at the start of the expiration phase.

In the parent branch of the realistic geometry, atsection 1R, the transverse velocity is 25% of axialvelocity at peak inspiration and expiration. Closer tothe bifurcation, at section 2R, the transverse velocity is30% of the axial velocity at peak flow. Transversevelocity is greater than axial velocity in the parentbranch at section 2R during periods of flow reversal.The transverse velocity measured in the right and leftdaughter branches is significantly different. In the leftdaughter branch at section 4R transverse velocityreached 59% of the axial velocity at peak flow, whereasonly minimal levels are recorded in the right daughterbranch at section 3R.

Qualitatively similar flow structures are observed atall four conditions tested (15 £ L/a £ 80, Re = 740,1480, and a = 4.3, 7.0). Shear layers are observed at allconditions. The duration of this counterflow increasesas the flow becomes more strongly unsteady, from14% of the cycle period at a = 4.3 to 22% at a = 7.0.At peak flow times, the velocity profile in the parentbranch is flatter for a = 7.0. Similar levels of trans-verse velocity are measured at all stations in bothbifurcation models for a = 4.3 and 7.0. For the twoReynolds numbers tested, the shear layers are presentin the bifurcation for the same duration, but thinnershear layers with higher velocity gradients are observedat the higher Reynolds number.

Figure 7a shows the fluctuation of axial velocityover multiple cycles at Point A (Fig. 1) on the center-line of the parent branch in the idealized bifurcationmodel. At peak expiration (negative velocity), a high-frequency fluctuation can be observed. The amplitudeof this velocity fluctuation is higher closer to flowdivider. Figure 7b shows the phase-averaged velocityover ten cycles.

DISCUSSION

The aim of this study is to enhance understanding oflocal convective flow mechanisms in a respiratorybifurcation during HFOV. Several previous authorshave reported pointwise velocity measurements inin vitro airway models using laser Doppler velocimetry

(LDV).17,24 Particle image velocimetry (PIV), as awhole-field technique, can potentially give clearerinsight into the spatial structure of the flow. Ramuzatand Riethmuller26 adopted PIV to study steady andoscillatory flows in airway models, and reported steadystreaming effects. Many previous studies of fluiddynamics in HFOV have been based on idealizedmodels of the airways, neglecting realistic geometricfeatures such as curvature, asymmetric branching, andnoncircular cross sections. However, the computationalwork of Nowak et al.22 identified significantly differentflow patterns in idealized and anatomically realisticairways under normal breathing conditions. Großeet al.11 highlighted the influence of geometric asymme-try of the realistic lung on normal respiratory airflow.

In the present work, two-component and stereo-scopic (three-component) PIV were used in both ide-alized and realistic bifurcation models. An idealizedgeometry model was used to facilitate clear identifica-tion of the generic fluid dynamic phenomena in themixing of inspired and expired air. An anatomicallyrealistic model was used to explore the additional ef-fects of realistic geometric features such as local cur-vature, nonuniform noncircular cross sections, andasymmetric branching angles.

0 1 2 3 4 5-1.5

-0.75

0

0.75

1.5

Dim

ensi

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ssV

eloc

ity

-1.5

-0.75

0

0.75

1.5

Dim

ensi

onle

ssV

eloc

ity

τ

0 1/2 1

τ

(a)

(b)

FIGURE 7. Axial velocity measured at Point A (Fig. 1) on thecenterline of the parent branch of the idealized model, (a) overmultiple cycles and (b) phase-averaged over ten cycles.

HERATY et al.1864

The most important observed flow phenomena aresketched in Fig. 8 for four key points in the cycle. Themain features of the flow are common to both the ide-alized and realistic models and to all four flow condi-tions modeled. Quasi-steady flow exists only at times ofpeak flow, as other authors have also observed.17

Counterflow at Flow Reversal

One of the significant findings of this study is thatinspiratory and expiratory fluid streams coexist in theairways for significant periods around flow reversal, asa result of the unsteadiness of the HFOV cycle. Ata = 7.0, counterflow and shear layers are present inboth models for longer than in the less strongly un-steady case, a = 4.3. At flow reversals in both models,shear layers appear between the inspiratory and expi-ratory streams. In the realistic model, these shear lay-ers persist for slightly longer in the wider left daughterbranch than in the right daughter branch. Vorticalstructures are apparent as a result of roll-up of shearlayers in both models, illustrated by instantaneousstreamlines shown in Fig. 5 and in the schematic dia-gram of Fig. 8.

Secondary Flow

The axial curvature of the idealized bifurcationresults in a velocity profile skewed toward the insidewall of the flow divider and the generation of second-ary flow structures in the daughter branches duringinspiration. Lieber and Zhao17 and Peattie andSchwarz24 observed similar flow structures in idealizedbifurcation geometries. Eckmann and Grotberg7

observed a skewed velocity profile in a curved tube.Secondary flow longitudinal vortical structures areobserved throughout the expiration phase and at flowreversal. Jan et al.14 visualized a similar flow structureduring the decelerating phase of expiration fora = 21.3 and L/a = 20. More recently Fresconi et al.8

observed a similar secondary flow pattern in the parent

branch during expiration in a similar idealized bifur-cation model. Significant levels of secondary flow areobserved in the daughter branches during inspirationand in the parent branch during expiration, as shownin Fig. 6 at sections 1W and 2W.

In the realistic geometry, significant levels of sec-ondary flow are observed during both inspiration andexpiration in both parent and daughter branches. Inthe realistic model the parent and daughter brancheshave slight three-dimensional axial curvature, thedaughter branches divide asymmetrically, and thewalls are nonparallel. The curvature and nonparallelwalls of the parent branch result in similar levels ofsecondary flow in the parent branch during inspirationand expiration, as seen in Fig. 6 at section 1R andsection 2R. In inspiration, the skewed velocity profileand local wall curvature at the entrance of the rightdaughter branch cause a recirculation region. Whilethe axial flow structure in the realistic bifurcation issimilar to that observed in the idealized bifurcation,the nonplanar walls and slight three-dimensional axialcurvature have a significant effect on the levels andstructure of secondary flow.

Although axial and secondary flow structures in theidealized and realistic models are very different, theinteraction between axial and secondary flow at flowreversals is similar in both models. In the parent branchof the realistic model, a single longitudinal vortex isobserved, along with other more complex structure.This contrasts with the system of four vortices observedin the idealized geometry. In both models, the second-ary flow vortices span the counterflowing inspiratoryand expiratory flows at flow reversal.

Flow Separation

Flow separation with recirculation is observed inboth the idealized and realistic bifurcation models atdifferent times in the HFOV cycle. Recirculation in therealistic geometry results from separation due to thelocal curvature of the inside wall of the right daughter

secondaryflow

counterflow

shear layerroll-up

early expiration peak expiration

secondaryflowsecondary

flowshear layer

roll-up

early inspiration

secondaryflow

peak inspiration

counterflow

flow separation

time

flowrate

FIGURE 8. Sketch of the major flow structures observed in airway bifurcations throughout the cycle.

Fluid Dynamics of Gas Exchange in HFOV 1865

branch during peak inspiration. In the idealized model,recirculation occurs on the outside of the bifurcationas the flow decelerates from peak inspiration, asshown in Fig. 3 for s = 0.452. Schroter and Sudlow29

studied steady flow in an idealized bifurcation for100 £ Re £ 4500, and observed that the presence ofrecirculation regions was a function of the tube radiusa of the parent branch and the radius of curvature Rc

of the parent and daughter branch centerlines. Theyobserved a region of recirculation in a model withRc @ a, but for Rc = 4a, no recirculation was ob-served. In the idealized geometry employed here,Rc = (5.4)a, and recirculation does not occur in thequasi-steady peak inspiration flow. Recirculation didnot occur at any time in low-frequency oscillationexperiments (L/a = 634, Re = 740, a = 1.08; resultsnot shown) in either geometry model. These observa-tions are consistent with the findings of Schroter andSudlow29 for steady flow. Thus, the transient flowseparation and recirculation observed in the presentwork appears to be an unsteady effect, dependent onWomersley number.

Instability

There is evidence of instability in the flow, in theform of high-frequency velocity fluctuations whichwere detected in the parent branch at peak expirationin the idealized geometry, as shown in Fig. 7a. Thesefluctuations vary from cycle to cycle, and do not ap-pear in the phase-averaged velocity shown in Fig. 7b.This is consistent with the findings of Peattie andSchwarz,24 who observed turbulent bursts in the parentbranch of an idealized bifurcation at peak expiration.

Similar velocity fluctuations were observed in therealistic model on the parent branch centerline, at bothpeak inspiration and peak expiration. The magnitudeof the fluctuations was highest near the flow divider inexpiration, when a recirculation region forms betweenthe fluid streams from the daughter branches. Thetemporal resolution of the PIV measurements in thisstudy allows fluctuations at up to 26–29 times the cyclefrequency to be resolved. As Peattie and Schwarz24

detected fluctuations at 10–100 times the ventilationfrequency, it is possible that some high-frequencyfluctuations were beyond the resolution of the presentexperiments.

Significance for Mass Transport

The experimental results presented here describe theHFOV velocity field and flow structures in detail.However, concentration fields and mass transporteffects have not been measured directly, and it is notpossible to draw firm conclusions about respiratory

mass transfer. Here we discuss the possible impact ofsome of the observed flow features on mass transportand gas exchange in HFOV, in light of previousresearch on mass transfer.

It is known that lateral mixing by secondaryflows can play an important role in mass transport.Eckmann and Grotberg,7 Fujioka et al.,9 Nishidaet al.,21 and Tanaka et al.30,31 have shown that effectivediffusion is greater in curved and/or bifurcated tubesthan in straight tubes for a range of conditions repre-sentative of HFOV, as a result of secondary flow.Tanaka et al.31 also showed that significant transversemixing occurred in an idealized model airway bifur-cation at flow reversal, and found that a pause in theflow waveform around reversal allowed more time fortransverse mixing, increasing the effective diffusivityby a factor of two. From these studies it is clear thatthe level of secondary flow has a significant effect onmass transport. Therefore, the enhanced levels of sec-ondary flow due to axial curvature, asymmetricbranching, and local wall curvature, measured in therealistic model in this study, could have importantimplications for mass transport in the lung. Theinteraction of secondary flow with axially counter-flowing streams may be a further mechanism to en-hance axial mass transport. However, this hypothesisrequires further investigation to test and quantify.

In the upper airways, Taylor-type dispersion is adominant mechanism.4,16 Taylor (or shear-augmented)dispersion occurs when a nonuniform velocity profilein the airway causes differential rates of axial convec-tion for fluid at different transverse locations.32,33 Atpeak flow, a flattened velocity profile is observed in theparent branch of the idealized and realistic bifurcationmodels, as shown in Fig. 3. However, in off-peak flow,the velocity profile in the parent branch is less uniformand hence more conducive to Taylor dispersion.

The transient flow separation observed in theseexperiments may act as a convective mechanism toenhance axial mixing in oscillatory flow. Fluid particleswhich get trapped in a recirculation region are detainedin the airway while the main stream passes by, andreleased for mixing later, when the flow separationbreaks down. Thus, recirculating particles are effec-tively transferred upstream relative to the bulk motionof the main axial fluid stream. Direct measurement orcomputation of the concentration field will be requiredin future work to test and quantify the overall effect ofthis phenomenon on mass transport, as for the otherflow phenomena discussed above.

Clinical Application

Acute lung injury and acute respiratory distresssyndrome (ALI/ARDS) are severe inflammatory

HERATY et al.1866

diseases of the lung, and have a high morbidity andmortality. In fact, the mortality attributable to ALI inthe United States is comparable to that seen with HIVinfection, breast cancer, and asthma.28 There is no curefor ALI/ARDS and the treatment is supportive. A keycomponent of this supportive therapy is the mechanicalsupport of respiration. Conventional mechanical ven-tilation strategies cause high lung stretch, and candamage lungs and contribute to mortality.1 This hasbeen a focus of intensive research effort in recent years,and has resulted in the development of ‘low-stretch’ventilatory strategies, which have been demonstratedto save lives.1

HFOV has been widely used in the clinical settingfor the management of the critically ill neonate andchild. HFOV is increasingly used in adults with severeacutely injured lungs, where it performs comparably toleading edge ‘protective’ ventilation strategies.1,6

However, our understanding of HFOV has advancedrelatively little since its introduction into clinicalpractice in the late 1970s.3 A better understanding ofthe mechanisms by which gas exchange occurs inHFOV offers the potential of developing more effec-tive HFOV support therapies, by enhancing gasexchange while minimizing the potential for lungdamage. Such novel HFOV strategies could signifi-cantly reduce death and disability from these devas-tating disease processes.

The research presented in this article offers new in-sights into the fluid dynamics of HFOV, which are aprerequisite for deep understanding of mass transportand gas exchange. In particular, the effect of complexrealistic geometry on flow features has been investi-gated. In future work, these experimental results willbe used to guide and validate high-resolution compu-tational models, incorporating O2 and CO2 diffusion.Models of this type may be used to explore the designspace for HFOV much more efficiently and safely thanin preclinical and clinical trials, leading to opportuni-ties for optimization of HFOV tidal volume, fre-quency, and waveform parameters.

Limitations

This study is based on in vitro models which havesome inherent limitations. The models are rigid, anddo not simulate dynamic deformations of the airwayduring the breathing cycle. However, this is a reason-able approximation for the upper conducting airway,in which deformation is restricted by the presence ofcartilage in the walls.23 A potentially more significantlimitation of the present work is that models consist ofa single tracheobronchial bifurcation. Previous studiesof HFOV in the upper airway have shown that the flow

structure in each bifurcation generation is influencedby the flow from higher and lower generations.30

However, in a single-generation model, clearer insightsinto local fluid dynamics are possible without theadded complexity of multigeneration effects. Thisfundamental approach was taken in the present workbecause a detailed understanding of flow in a singlegeneration is a prerequisite for understanding ofHFOV mechanisms in the lung as a whole.

CONCLUSION

In summary, we have shown that around times offlow reversal, inspiratory and expiratory flows co-existthroughout the bifurcation for substantial periods ofthe oscillatory cycle, and the duration of this coun-terflow increases as the oscillation frequency increases.Shear layers form between these counterflowingstreams, leading to the formation of vortices, whichcould enhance mixing between the streams. Secondaryflows, due to airway curvature and the flow betweenparent and daughter branches, also mix the inspiratoryand expiratory streams. Unsteady flow separation andrecirculation occur in both geometric models, at or justafter peak flow, although it appears to be highlygeometry dependent. Secondary flow velocity is sig-nificant in comparison with axial velocity at manytimes throughout the cycle, and greater than it in somecases near reversal. Secondary flow velocities arehigher in the realistic geometry than in the idealizedgeometry, because of wall curvature. In the idealizedgeometry, the secondary flow in the parent branchresembles classical Dean vortices, but it is more com-plex in the realistic geometry. Axial velocity profilesare relatively flat at peak flow and most nonuniform attimes of off-peak flow.

Understanding of the fluid dynamic mechanismswhich underlie HFOV may ultimately contribute to thedevelopment of HFOV strategies to achieve moreeffective gas exchange, and ultimately increase survivalin sufferers from ALI/ARDS. This work highlights theimportance of transient counterflow, secondary flow,and recirculation, and also shows that realistic geom-etry features have a significant effect.

ACKNOWLEDGMENTS

The authors are grateful to Ms. Sue Harty andDr. Gerard O’Sullivan of the Merlin Park ImagingCentre for providing CT images of the models. We alsothank Mr. Colm Walsh and Mr. Kumar Saidha fortheir contributions to the development of the flow

Fluid Dynamics of Gas Exchange in HFOV 1867

apparatus. This research was supported by the IrishResearch Council for Science, Engineering and Tech-nology, funded by the National Development Plan; theProgramme for Research in Third Level Institutions;and National University of Ireland, Galway throughthe Millennium Research Fund.

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