J Appl Physiol 96: 2109–2114, 2004.
First published February 13, 2004; 10.1152/japplphysiol.00540.2003.
Nasal cavity dimensions in guinea pig and rat measured
by acoustic rhinometry and fluid-displacement method
Sune P. Straszek and Ole F. Pedersen
Department of Environmental and Occupational Medicine, University of Aarhus, DK-8000 Aarhus, Denmark
Submitted 20 May 2003; accepted in final form 10 February 2004
nasal airway volume; nasal obstruction; airway pharmacology; perfluorocarbon
no published studies applying AR in rats, we included this
animal because it may be a potential study object.
MATERIALS AND METHODS
Care and Use of Animals
Research, investigations, and care of animals has been in accordance to American Physiological Society’s Guiding Principles in the
Care and Use of Animals. The protocol was approved by the Danish
Regulations for Use of Laboratory Animals.
AR
We used a system (GJ Elektronik, Skanderborg, Denmark) slightly
modified from the one described by Pedersen et al. (15). A sound
pulse propagates through a sound tube with an internal diameter of 4
mm, passes a microphone, and enters the nasal cavity via a funnelshaped nosepiece. The reflected waves travel back through the tube
and are recorded by the microphone connected to an amplifier (GJ
Elektronik) and via an analog-to-digital converter (PC-Card Das16/
12, Computer Boards, MA) sampled by a computer (700 MHz
Armada, Compaq) at 100,000 Hz. Measurements are displayed as an
area-distance curve, where area is a function of distance with 1.72 mm
between sampling points. Before measurements in the animals, the
system was calibrated by use of two rigid plastic tube models with
step changes of cross-sectional areas and minimum areas of 0.02 cm2,
a worst-case model of small-animal nasal cavities. One acoustic
measurement in this study always consisted of 5–10 curves of each
side of the cavity, each curve made from averaging 10 consecutive
sound pulse responses.
FDM
The nasal cavity is placed with the axis of the nasal cavity in a
vertical position. It is filled from below with perfluorocarbon through
the nostril by a constant flow from a Harvard pump. Changes in the
slope of the pressure-time curve at the inlet is proportional to changes
in the cross-sectional areas of the nasal cavity with distance. Pressure
is measured consecutively at every 0.5 s. For a detailed description of
the fluid-displacement-method, physical properties of perfluorocarbon, and potential errors, we refer to a previous study by Straszek et
al. (17). A moving-average algorithm was applied to reduce noise in
the measurements. We used two consecutive moving averages of five
and three samples for guinea pigs, and a single moving average of
three samples for rats.
(AR) is increasingly used to evaluate
pharmaceutical compounds with effect on the nasal mucosa. A
number of studies used guinea pigs (5, 6, 12–16), cats (2,
9–11), or dogs (7, 8) as models for testing mucosa active
substances in the nasal cavity. There have so far been few
attempts to validate AR by comparison to other methods,
including nasal casting, fluid displacement, and magnetic resonance imaging. Kaise et al. (6) estimated that AR only
measured 70% of nasal cavity volume in guinea pigs, and data
by Straszek et al. (17) suggest that it measures 88% in dogs and
71% in cats. In the present study, we validated AR postmortem
in guinea pigs and rats by comparison to a previously described
fluid-displacement method (FDM) (3). We wanted to quantify
AR measurement errors in small laboratory animals used in
comparative pharmacological evaluations. Although there are
Guinea pigs. We used five female Dunkin Hartley guinea pigs
(weight 394–522 g), injected intraperitoneally with a lethal dose of 1
ml pentobarbital sodium (50 mg/ml) and decapitated before the
experiments. We made a nosepiece, as described by Pedersen et al.
(15), from two pipette tips so that a sleeve was formed to which
Address for reprint requests and other correspondence: S. P. Straszek, Dept.
of Environmental and Occupational Medicine, Univ. of Aarhus, Vennelyst
Blvd. 6, DK-8000 Aarhus, Denmark (E-mail: [email protected]).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
ACOUSTIC RHINOMETRY
http://www.jap.org
Experimental Protocol
8750-7587/04 $5.00 Copyright © 2004 the American Physiological Society
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Straszek, Sune P., and Ole F. Pedersen. Nasal cavity dimensions
in guinea pig and rat measured by acoustic rhinometry and fluiddisplacement method. J Appl Physiol 96: 2109–2114, 2004. First
published February 13, 2004; 10.1152/japplphysiol.00540.2003.—
The purpose of the study was to measure nasal passageway dimensions in guinea pigs and rats by use of acoustic rhinometry (AR) and
by a previously described fluid-displacement method (FDM)
(Straszek SP, Taagehoej F, Graff S, and Pedersen OF. J Appl Physiol
95: 635–642, 2003) to investigate the potential of AR in pharmacological research with these animals. We measured the area-distance
relationships by AR of nasal cavities postmortem in five guinea pigs
(Duncan Hartley, 400 g) and five rats (Wistar, 250 g) by using
custom-made equipment scaled for the purpose. Nosepieces were
made from plastic pipette tips and either inserted into or glued onto
the nostrils. We used liquid perfluorocarbon in the fluid-displacement
study, and it was carried out subsequent to the acoustic measurements.
We found for guinea pigs that AR measured a mean volume of 98
mm3 (95–100 mm3) (mean and 95% confidence interval) of the first
2 cm of the cavity. FDM measured a mean volume of 146 mm3
(117–175 mm3), meaning that AR only measured 70% (50–90) of the
volume by FDM. For rats, the volume from 0 to 2 cm was 58 mm3
(55–61 mm3) by AR and 73 mm3 (60–87 mm3) by FDM, resulting in
AR only measuring 83% (66–100%) of volume by FDM (see Table
2). We conclude that absolute nasal cavity dimensions are underestimated by AR in guinea pigs and rats. This does not preclude that
relative changes may be correctly measured. In vivo trials with AR
using rats have not yet been published. The FDM is possibly the most
accurate alternative to AR for measurements of the nasal cavity
geometry in small laboratory animals, but it can only be used postmortem.
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NASAL CAVITY DIMENSIONS IN GUINEA PIG AND RAT
RESULTS
Test Models
Figure 3 shows the results of the measurements on the test
models. AR does not portray sudden area changes as accurately
as FDM in model 1, but there is no systematic difference. For
model 2, which is constricted over a longer distance, AR seems
to underestimate the area behind the constriction slightly.
Guinea Pigs
suction is applied through an injection cannula. In guinea pigs, this
opens the nasal passageway and secures a tight seal of the nostril. The
head was placed with the nasal cavity in the horizontal plane with the
back of the nose upward (Fig. 1). Five acoustic measurements were
obtained with alternating measurements on each nostril. The sound
waves travel through the cavity, reach the end of the nasal septum, and
continue backward through the contralateral cavity as well as forward
into a common conduit leading to the nasopharynx. AR beyond the
septum thus measures the sum of the cross-sectional areas of the
common conduit as well as the contralateral cavity.
The fluid-displacement study was carried out on all guinea pigs
immediately after the acoustic measurements. Two conical pipette tips
were cut at a suitable diameter and glued (Cyanoacrylate, NDO
Superlim, Norden Olje, Hadsund, Denmark) around each nostril. They
were connected one at a time to a Harvard pump delivering a constant
flow of 0.0063 ml/s in a way so that resistance would be kept to a
minimum (Fig. 2). Five consecutive FDM measurements were performed with the opposite nostril blocked, and hereby filling the entire
cavity completely, before fluid rose through the nasopharynx and ran
out of the mouth or the open larynx or pharynx. Measurements
corrupted by air bubbles in the nasal cavity were discarded. FDM was
always done with the contralateral cavity filled with fluid, thus
measuring only the cross-sectional area of the common conduit after
the fluid surface had passed the end of the nasal septum.
Rats. We used male Wistar rats (weight 234–285 g) killed with 1
ml of pentobarbital sodium (50 mg/ml) intraperitoneally. It was not
possible to apply the nosepieces as described for guinea pigs, because
the narrow nostrils closed on suction. Instead we used the same
technique as for fluid displacement: a few millimeters were cut off of
two pipettes so they had an opening cross-sectional area of ⬃7.5 mm2.
They were glued to each nostril so that a fluid-tight transition from
nosepiece to nostril was achieved. After decapitation, the head was
placed in a supine position as described for the guinea pigs, and
acoustic measurements were done. FDM was subsequently carried out
as described above (Fig. 2).
J Appl Physiol • VOL
Fig. 2. Setup for fluid-displacement method (FDM) measurements of nasal
cavities in guinea pigs and rats. From a syringe driven by a Harvard pump,
perflourocarbon with a constant but very slow flow enters the nasal cavity via
a nosepiece glued onto the nostril. The pressure is measured through an
air-filled branch of the tube. The location of the animal’s nose is at the top
right.
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Fig. 1. Setup for acoustic rhinometry (AR) measurements of nasal cavities of
guinea pigs and rats. The sound tube is connected to the nostril through a
nosepiece (2 joined pipette tips). Suction is applied through a cannula inserted
into the space between 2 layers of the nosepiece, creating a sleeve around the
nostril. This secures a tight seal and opening of the nostril (see inset). Only the
location of the head is indicated.
An individual area-distance curve is shown in Fig. 4. The
nasal cavity starts at 0 cm where the nosepiece depicted in Fig.
1 opens into the nostril. The high repeatability of both AR and
FDM measurements appies to all animals used. At a depth of
⬃2 cm, the nasal septum terminates, and fluid rises through the
rhinopharynx common to both sides. In Fig. 5, data from all
five guinea pigs (10 cavities) were pooled. Figure 5 shows
mean area-distance curves for both acoustic measurements and
fluid displacement along with 95% confidence intervals (CI) of
the mean. The minimum cross-sectional area (95% CI) is a few
millimeters inside the cavity, and it is measured to be 0.019
cm2 (0.017–0.022 cm2) by AR, and 0.054 cm2 (0.037–0.070
cm2) cm2 by FDM (Fig. 5). AR measures smaller crosssectional areas compared with FDM in the distance interval
from 0 to 2 cm but higher cross-sectional areas beyond 2 cm.
CIs are also narrower for AR than FDM. At ⬃2 cm, the nasal
septum dividing the cavity comes to an end. This was confirmed by dissection that revealed an anatomic defect in the
lower part of the nasal septum at this point. The mean crosssectional area there was 0.094 cm2 measured by AR.
The mean nasal cavity volume (95% CI) from the end of the
nosepiece and 2 cm into the cavity was calculated from FDM
measurements and found to be 146 mm3 (117–175 mm3). AR
measured 98 mm3 (95–100 mm3), which means that volume by
AR measures 70% (50–90%) of the volume measured by FDM
(Table 1). There was no significant difference between sides or
correlation between individual minimum areas and corresponding cavity volume.
NASAL CAVITY DIMENSIONS IN GUINEA PIG AND RAT
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Fig. 3. Measurements by AR and FDM on 2 models consisting
of joined plastic tubes with cross-sectional areas between 0.02
and 0.075 cm2. The filter algorithm applied to FDM is the same
as the one used in the guinea pig experiments (see text).
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Fig. 4. For guinea pig 4, left side, cross-sectional area measured by AR (n ⫽ 5 measurements) and FDM (n ⫽ 5 measurements) as a function of distance is shown. The 95% confidence
interval by AR is also shown as lines without symbols. The
nasal cavity begins at distance ⫽ 0 cm. The nasal septum
terminates at a distance of ⬃2 cm. The contralateral cavity is
filled with fluid during FDM but open during AR.
Fig. 5. For all guinea pigs, mean cross-sectional areas from all
cavities (n ⫽ 10 cavities) measured by AR and FDM as a
function of distance are shown. The 95% confidence intervals
for AR and FDM are shown as lines without symbols.
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Table 1. Volume determined by acoustic rhinometry and fluid-displacement method in guinea pigs
Volume by AR, mm3
(AR/FDM) ⫻ 100%
Volume by FDM, mm3
Guinea Pig No.
Left
Right
(Left ⫹ Right)
Left
Right
(Left ⫹ Right)
(Left ⫹ Right)
1
2
3
4
5
Mean⫾95% CI
97
93
98
96
104
98⫾5
95
96
97
102
103
99⫾4
192
189
195
198
207
196⫾8
115
128
149
196
161
150⫾40
122
152
69
211
161
143⫾64
237
280
218
407
322
293⫾93
81
68
89
49
64
70⫾20
Values are left, right, and total (left⫹right) volumes of nasal cavities for both acoustic rhinometry (AR) and fluid-displacement method (FDM). Volumes are
measured from the end of the nosepiece to 20 mm inside the cavity (see text). CI, confidence interval.
Rats
DISCUSSION
In General
This study compared measurements obtained postmortem.
There is reason to believe that some physiological changes take
Fig. 6. For rat 3, right side, cross-sectional area measured by
AR (n ⫽ 5 measurements) and FDM (n ⫽ 4 measurements) as
a function of distance is shown. The 95% confidence interval by
AR is also shown as lines without symbols. One FDM measurement was discarded due to air bubbles in the cavity. The
nasal cavity starts at distance ⫽ 0 cm. Note that nosepieces for
the rat were different in AR and FDM measurements. To
demonstrate the abrupt termination of the septum, fluid was in
this case allowed to leak through an empty contralateral cavity,
which caused the abrupt rise in cross-sectional area as the nasal
septum terminates at 2.23 cm. The origin of the sharp rise and
fall in cross-sectional area at distance ⫽ 1.8 cm is discussed in
the text.
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An individual area-distance curve is shown in Fig. 6. The
cavity starts at 0 cm and ends at ⬃2.2 cm. Around 1.85 cm into
the cavity, FDM rises sharply and falls again. This phenomenon is only seen in some of the cavities and to a varying
degree. The measurements were continued until fluid reached
the point where the airway was cut or until fluid ran out
through the mouth. Data from all five rats (9 cavities) were
pooled and are presented in Fig. 7. One cavity was obstructed
by glue and could not be reopened. Minimum cross-sectional
area (95% CI) of all cavities was 0.017 cm2 (0.016–0.018 cm2)
by AR and 0.028 cm2 (⫺0.05–0.11 cm2) by FDM. Between
animals, variation in AR is minimal, but larger for FDM
measurements, especially at the start and end of the nasal
septum. FDM produces fairly consistent measurements in the
middle part of the cavity, but fluid reaches the nasal septum
after 1.9–2.1 cm depending on the animal, and the FDM 95%
confidence intervals consequently widen considerably.
Mean volume (95% CI) in a 2.0-cm distance interval starting
from the opening of the nostril was found to be 73 mm3 (59–86
mm3) for FDM and 58 mm3 (55–61 mm3) for AR (Table 2).
Thus AR measures 83% (66–100%) of the volume measured
by FDM. No correlation was found between individual minimum area and corresponding cavity volume.
place shortly after death. However, the aims of this study were
to validate how AR measures the complex geometry of nasal
cavities in small laboratory animals and to investigate the
methodological aspects for future in vivo comparative pharmacological studies. Studies in guinea pigs show that only 70%
of the cross section is measured. We believe that AR can
measure relative changes in rats, as has been shown to be the
case in guinea pigs (5, 6, 12–16). When the curves obtained on
the models and the individual animals are compared, it is seen
(Figs. 4 and 6) that FDM has a higher resolution than AR, in
terms of both distance (more points per distance unit) and
cross-sectional area. Other explanations for the difference
between AR and FDM in terms of cross-sectional areas and
volumes have previously been discussed by Straszek et al. (17).
A number of assumptions concerning planar waves, symmetric
structure, and minimal losses inside the cavity may be violated,
and the errors increase with distance into the cavity. Other
factors can theoretically contribute, including recesses only
accessible to fluid, and deformation of the nasal passageways
due to fluid pressure, which, however, is minimal. A constriction with a cross-sectional area below a certain threshold may
result in severe underestimation by AR of the cross-sectional
areas beyond the constriction (4). This is indicated in the
narrower of the two models (Fig. 3). The exact value of the
threshold area is not known, but it is most likely below 0.01
cm2. Finally, a combination of errors, including capillary
effects in the nostril and slight differences in position of the
head in relation to the direction of gravity (18), may contribute
to the differences but are considered of lesser importance (17).
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Fig. 7. In all rats, mean cross-sectional area from all cavities
(n ⫽ 9 cavities) measured by AR and FDM related to distance
is shown. The 95% confidence intervals for AR and FDM are
shown as lines without symbols. One cavity is excluded because the nostril could not be opened after the nosepiece had
been glued around it.
Guinea Pigs
Rats
The same considerations expressed for the guinea pigs
regarding comparability of AR and FDM also apply to the
rat study. However, rats have a narrower but longer nasal
cavity than guinea pigs, and their internal structures possibly reflect sound waves with greater loss. In Fig. 6, FDM
measured a spike of ⬍0.5 cm from the end of the septum,
which was not seen by AR. This is likely because of lower
spatial resolution of AR and a recess being filled through an
orifice only detectable by FDM. This spike was observed in
several cavities, but not all, and contributes to the large
confidence interval at this distance (see Fig. 7).
The mean volumes measured by FDM, 72 mm3 (58–86
mm3), and by AR, 58 mm3 (55–61 mm3), contained in the
first 2 cm of the nasal cavity are theoretically large enough
Conclusion
The main findings are an underestimation of cross-sectional areas by AR compared with FDM, both in guinea pigs
Table 2. Volume determined by AR and FDM in rats
Volume by AR mm3
(AR/FDM) ⫻ 100%
Volume by FDM mm3
Rat No.
Left
Right
(Left ⫹ Right)
Left
Right
(Left ⫹ Right)
(Left ⫹ Right)
1
2
3
4
5
Mean⫾95% CI
62
55
58
58
*
58⫾5
65
55
57
53
55
57⫾6
127
120
115
111
110
117⫾9
109
66
74
62
*
78⫾34
80
82
75
45
58
68⫾20
189
148
149
107
116
142⫾40
67
81
77
104
95
85⫾19
Values are left, right, and total (left⫹right) volumes of nasal cavities for both AR and FDM. Volumes are measured from the end of the nosepiece to 20 mm
inside the cavity. *Measurements could not be obtained from 1 nostril.
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Both AR and FDM showed very good repeatability. However, the differences between animals were much greater for
FDM than for AR (Fig. 5), probably due to higher spatial
resolution of FDM in detecting individual differences.
Our results correspond well with the findings of Kaise et al.
(6), despite the fact that they used impression material to
estimate the nasal cavity dimensions instead of FDM. The
guinea pig appears suited for acoustic measurements because a
volume of 146 mm3 leaves enough space for intranasal application of compounds diluted in vehicle. This is supported by
results from earlier in vivo experiments on guinea pigs (5,
12–16).
for vehicle, e.g., 10–20 ␮l (mm3). However, the crosssectional area at 2-cm distance, 0.035 cm2 (0.019–0.05
cm2), is only 37% compared with the area in guinea pigs.
Because the minimum cross-sectional areas by AR were
similar in guinea pigs and rats, a difference here cannot
explain the discrepancy between the measured volumes
behind the narrowing. Future prospects include development of new algorithms, more sensitive microphones measuring higher frequencies, and optimal relationship between
sound tube dimensions and the cavity measured (1). In that
way, it may be possible to reduce the signal-to-noise ratio
and make measurements of higher resolution. The suction
device did not work in rats, but gluing a nosepiece to the
nostril was a solution that produced consistent measurements and still allows substances to be applied through the
nostrils with a pipette tip. Because of the type of glue,
however, survival studies will hardly be possible before a
new and better design of nosepiece has been developed. To
examine even smaller animals, we tried to measure mice in
our experiments. However, we discarded the measurements
because of methodological difficulties, including a toonarrow nostril for satisfactory readings, both with AR and
FDM. We estimated the volume of a nasal cavity to be 25
␮l, hardly enough for intranasal application of pharmacological compounds, although it cannot be excluded with
future technical development.
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and rats. In previous studies (5, 6, 12–16), it has been
possible to measure relative changes in guinea pig nasal
congestion. On the basis of these studies, we believe this is
also possible in the rat. Both species have a nasal cavity
volume large enough for intranasal application of mucosa
active substances, making them interesting to pharmacological evaluation studies. Fluid displacement has a high repeatability, and it is possibly the closest we can get to
estimate the true nasal cavity geometry in small laboratory
animals.
ACKNOWLEDGMENTS
We thank Soren Nielson (University of Aarhus) for handling the animals.
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