Acoustic rhinometry: validation by three-dimensionally reconstructed computer tomographic scans.

The aim of the present study was a validation of acoustic rhinometry (AR) by computed tomography (CT). Six healthy subjects were examined by CT and AR. The CT data were processed in a computer program (AutoCAD), and a virtual three-dimensional model of each nasal cavity was constructed. This model permitted an individual prediction of the center line of the sound wave propagation through the air volume of the nasal cavity with the cross-sectional areas oriented perpendicularly to this line. The area-distance curves derived from AR and CT were compared. Linear regression analysis revealed a reasonable agreement of AR and CT in the anterior nose below a mean of 6 cm distance from the nostrils [r = 0.839, P < 0.01, m = 1.123, b = -0.113 (AR = m x CT + b)]. The measuring accuracy using CT as gold standard revealed a mean error at the nasal valve of <0.01 cm(2) (4.52%) and at the nasal isthmus of 0.02 cm(2) (1. 87%). Beyond 6 cm, the correlation decreased (r = 0.419), and overestimation of the true area occurred (>100%). In conclusion, the measurements were reasonably accurate for diagnostic use up to the turbinate head region. Certain factors induce an overestimation of the true areas beyond this region. However, these factors are constant and reproducible in a single subject, and intraindividual comparative measurements are possible beyond the turbinate head region.     

Atrophic rhinitis: a CFD study of air conditioning in the nasal cavity.

Atrophic rhinitis is a chronic disease of the nasal mucosa. The disease is characterized by abnormally wide nasal cavities, and its main symptoms are dryness, crusting, atrophy, fetor, and a paradoxical sensation of nasal congestion. The etiology of the disease remains unknown. Here, we propose that excessive evaporation of the mucous layer is the basis for the relentless nature of this disease. Airflow and water and heat transport were simulated using computational fluid dynamics (CFD) techniques. The nasal geometry of an atrophic rhinitis patient was acquired from computed tomography scans before and after a procedure to narrow the nasal cavity. Simulations of air conditioning in the atrophic nose were compared with similar computations performed within the nasal geometries of four healthy humans. The excessively wide cavity of the patient generated abnormal flow patterns, which led to abnormal patterns of water fluxes across the wall. Geometrically, the atrophic nose had a much lower surface area than the healthy nasal passages, which increased water fluxes per unit area. Nevertheless, the simulations indicated that the atrophic nose did not condition inspired air as effectively as the healthy geometries. These simulations of water transport in the nasal cavity are consistent with the hypothesis that excessive evaporation of mucus plays a key role in the pathophysiology of atrophic rhinitis. We conclude that the main goals of a surgery to treat atrophic rhinitis should be 1) to restore the original surface area of the nose, 2) to restore the physiological airflow distribution, and 3) to create symmetric cavities.     

Comparison of glottic areas measured by acoustic reflections vs. computerized tomography

We compared measurements of glottic area obtained by acoustic reflection technique with anatomically equivalent area measured from computerized tomographic (CT) scans of the neck in 11 subjects with glottic pathology. Both measurements were performed in the supine position during tidal breathing at functional residual capacity. We found excellent agreement in glottic areas obtained by both methods: the mean (+/- SD) values were 1.8 +/- 0.8 cm2 for the acoustic method and 1.7 +/- 0.9 cm2 for the CT method. Linear regression analysis revealed the following relationship between the area measured by acoustic technique (AAC) and that measured by CT (ACT): AAC = 0.81.ACT + 0.36. There was a significant correlation between the two measurements of glottic area (r = 0.95, P less than 0.0001). We conclude that the acoustic reflection technique may be used reliably in clinical and physiological studies concerned with glottic geometry.     

Acoustic rhinometry in humans: accuracy of nasal passage area estimates, and ability to quantify paranasal sinus volume and ostium size.

A comprehensive study that compared acoustic rhinometry (AR) data to computed tomography (CT) data was performed to evaluate the accuracy of AR measurements in estimating nasal passage area and to assess its ability of quantifying paranasal sinus volume and ostium size in live humans. Twenty nasal passages of 10 healthy adults were examined by using AR and CT. Actual cross-sectional areas of the nasal cavity, sinus ostia sizes, and maxillary and frontal sinus volumes were determined from CT sections perpendicular to the curved acoustic axis of the nasal passage. Nasal cavity volume (from nostril to choana) calculated from the AR-derived area-distance curve was compared with that from the CT-derived area-distance curve. AR measurements were also done on pipe models that featured a side branch (Helmholtz resonator of constant volume but two different neck diameters) simulating a paranasal sinus. In the anterior nasal cavity, there was good agreement between the cross-sectional areas determined by AR and CT. However, posterior to the sinus ostia, AR overestimated cross-sectional area. The difference between AR nasal volume and CT nasal volume was much smaller than the combined volume of the maxillary and frontal sinuses. The results suggest that AR measurements of the healthy adult nasal cavity are reasonably accurate to the level of the paranasal sinus ostia. Beyond this point, AR overestimates cross-sectional area and provides no quantitative data for sinus volume or ostium size. The effects of paranasal sinuses and acoustic resonances in the nasal cavity are not accounted for in the present AR algorithms.     

Acoustic reflections during rhinometry: spatial resolution and sound loss

The accuracy ofthe acoustic reflections method for the evaluation of human nasalairway geometry is determined by the physical limitations of thetechnique and also by the in vivo deviations from the assumptions ofthe technique. The present study 1)examines the sound loss caused by nonrigidity of the nasal mucosa andviscous loss caused by complex geometry and its influence on theestimation of the acoustic area-distance function;2) examines the optimal relation between sampling frequency and low-pass filtering, and 3) evaluates advantages of breathingHe-O₂ during the measurements onaccuracy. Measurements made in eight plastic models, withcavities exactly identical to the "living" nasal cavities,revealed only minor effects of nonrigidity of the nasal mucosa. Thiswas confirmed by an electrical analog model, based on laser vibrometryadmittance measurements of the nasal mucosa, which indicated that theerror in the acoustic measurements caused by wall motion isinsignificant. The complex geometry of the nasal cavity per se (i.e.,departure from circular) showed no significant effects on themeasurements. Low-pass filtering of the signal is necessary to cut offcross modes arising in the nasal cavity. Computer simulations andmeasurements in models showed that the sampling frequency should beapproximately four times the low-pass filtering frequency (i.e., twicethe Nyquist frequency) to avoid influence on the result. No advantagewas found for the the use of He-O₂vs. air in the nasal cavity.

     

The effect of exercise on nasal uptake of ozone in healthy human adults.

The nose may help protect the lower respiratory tract from the effects of ambient ozone by scrubbing ozone from inspired air. Reductions in both nasal resistance and nitric oxide production with exercise may influence the efficiency of ozone uptake in the nose. Nasal ozone uptake was measured in 10 healthy volunteers before and after 15 min of moderate bicycle exercise. Ozone (0.2 parts/million) was pulled through both nostrils and out of the mouth at a constant flow while the subjects closed their epiglottises. Nasal uptake of ozone was determined by comparing the ozone concentration entering the nostrils to that exiting the mouth. Average preexercise uptake of ozone was 56 +/- 7.8 and 37 +/- 4.9% at 10 and 20 l/min, respectively. These averages did not significantly differ from those immediately postexercise (55 and 37%). Nasal ozone uptake increased significantly (P < 0.001) with decreasing flow rate, but intersubject variability in uptake could not be predicted by nasal volume or cross-sectional areas (as measured by acoustic rhinometry) or endogenous nitric oxide production. However, the percent change in ozone uptake after exercise, within an individual, was correlated with both 1) percent change in nasal volume (r = 0.70 at 10 l/min) and 2) percent change in the rate of volumetric expansion between the nasal valve and turbinates (r = 0.82 at 10 l/min). These results may be useful for assessing human risk associated with ozone exposure during exercise.     

THE SPERM WHALE'S NOSE: SEXUAL SELECTION ON A GRAND SCALE?1

The world's largest nose belongs to the sperm whale, yet its functional significance remains equivocal. In order to help shed light on its function, the head of a postmortem neonate sperm whale was subjected to CT scanning. Geometric comparisons between homologous cephalic structures in sperm whales and dolphins (normalized for body size) show extreme hypertrophy and size sexual dimorphism in the sperm whale's lipid spermaceti organ. Anatomic geometry, energetics, and behavior suggest that this immense nasal apparatus is a bioacoustical machine. Sexual selection via an acoustic display is suggested as an explanation for the size and continuous (physiologically isolated) energy investment in the construction and maintenance of the male's spermaceti organ.     

A technique to measure the ability of the human nose to warm and humidify air.

To assess the ability of the nose to warm and humidify inhaled air, we developed a nasopharyngeal probe and measured the temperature and humidity of air exiting the nasal cavity. We delivered cold, dry air (19-1 degrees C, <10% relative humidity) or hot, humid air (37 degrees C, >90% relative humidity) to the nose via a nasal mask at flow rates of 5, 10, and 20 l/min. We used a water gradient across the nose (water content in nasopharynx minus water content of delivered air) to assess nasal function. We studied the characteristics of nasal air conditioning in 22 asymptomatic, seasonally allergic subjects (out of their allergy season) and 11 nonallergic normal subjects. Inhalation of hot, humid air at increasingly higher flow rates had little effect on both the relative humidity and the temperature of air in the nasopharynx. In both groups, increasing the flow of cold, dry air lowered both the temperature and the water content of the inspired air measured in the nasopharynx, although the relative humidity remained at 100%. Water gradient values obtained during cold dry air challenges on separate days showed reproducibility in both allergic and nonallergic subjects. After exposure to cold, dry air, the water gradient was significantly lower in allergic than in nonallergic subjects (1,430 +/- 45 vs. 1,718 +/- 141 mg; P = 0.02), suggesting an impairment in their ability to warm and humidify inhaled air.     

Effects of the nasal valve on acoustic rhinometry measurements: a model study.

The influence of nasal valve on acoustic rhinometry (AR) measurements was evaluated by using simple nasal cavity models. Each model consisted of a cylindrical pipe with an insert simulating the nasal valve. The AR-determined cross-sectional areas beyond the insert were consistently underestimated, and the corresponding area-distance curves showed pronounced oscillations. The area underestimation was more pronounced in models with inserts of small passage area. The experimental results are discussed in terms of theoretically calculated "sound-power reflection coefficients" for the pipe models. The reason for area underestimation is reflection of most of the incident sound power from the barrier at the front junction between the pipe and the insert. It was also demonstrated that the oscillations are due to low-frequency acoustic resonances in the portion of the pipe beyond the insert. The results suggest that AR does not provide reliable information about the cross-sectional areas of the nasal cavity posterior to a significant constriction, such as pathologies narrowing the nasal valve area. When the passage area of the nasal valve is decreased, the role of AR as a diagnostic tool for the entire nasal cavity becomes limited.     

Effects of Localized Hydrophilic Mannitol and Hydrophobic Nelfinavir Administration Targeted to Olfactory Epithelium on Brain Distribution

Many nasally applied compounds gain access to the brain and the central nervous system (CNS) with varying degree. Direct nose-to-brain access is believed to be achieved through nervous connections which travel from the CNS across the cribriform plate into the olfactory region of the nasal cavity. However, current delivery strategies are not targeted to preferentially deposit drugs to the olfactory at cribriform. Therefore, we have developed a pressurized olfactory delivery (POD) device which consistently and non-invasively deposited a majority of drug to the olfactory region of the nasal cavity in rats. Using both a hydrophobic drug, mannitol (log P = -3.1), and a hydrophobic drug, nelfinavir (log P = 6.0), and POD device, we compared brain and blood levels after nasal deposition primarily on the olfactory region with POD or nose drops which deposited primarily on the respiratory region in rats. POD administration of mannitol in rats provided a 3.6-fold (p < 0.05) increase in cortex-to-blood ratio, compared to respiratory epithelium deposition with nose drop. Administration of nelfinavir provided a 13.6-fold (p < 0.05) advantage in cortex-to-blood ratio with POD administration, compared to nose drops. These results suggest that increasing the fraction of drug deposited on the olfactory region of the nasal cavity will result in increased direct nose-to-brain transport.     

A new nasal acoustic reflection technique to estimate pharyngeal cross-sectional area during sleep.

The conventional acoustic reflection technique in which acoustic waves are launched through the mouth cannot be applied during sleep, nor can it be applied to the nasopharynx, which is the major site of occlusion in patients with obstructive sleep apnea syndrome. We propose a new technique of nasal acoustic reflection to measure pharyngeal cross-sectional areas including the nasopharynx. The acoustic waves are introduced simultaneously to both nostrils during spontaneous nasal breathing. A new algorithm takes into account the nasal septum with asymmetric nasal cavities on both sides and assumes prior knowledge of the cross-sectional area of the nasal cavities and the position of the nasal septum. This method was tested on an airway model with a septum and on healthy human subjects. The conventional technique gave inaccurate measurements for pharyngeal cross-sectional areas for an airway model with asymmetric branching, whereas the new technique measured them almost perfectly. The oro- and hypopharyngeal cross-sectional area measurements acquired by the new method were not different from those obtained by the conventional method in normal subjects. This new method can be used as a monitor of upper airway dimensions in nocturnal polysomnography.     

Numerical Simulation of Airway Dimension Effects on Airflow Patterns and Odorant Deposition Patterns in the Rat Nasal Cavity

The sense of smell is largely dependent on the airflow and odorant transport in the nasal cavity, which in turn depends on the anatomical structure of the nose. In order to evaluate the effect of airway dimension on rat nasal airflow patterns and odorant deposition patterns, we constructed two 3-dimensional, anatomically accurate models of the left nasal cavity of a Sprague-Dawley rat: one was based on high-resolution MRI images with relatively narrow airways and the other was based on artificially-widening airways of the MRI images by referencing the section images with relatively wide airways. Airflow and odorant transport, in the two models, were determined using the method of computational fluid dynamics with finite volume method. The results demonstrated that an increase of 34 µm in nasal airway dimension significantly decreased the average velocity in the whole nasal cavity by about 10% and in the olfactory region by about 12% and increased the volumetric flow into the olfactory region by about 3%. Odorant deposition was affected to a larger extent, especially in the olfactory region, where the maximum odorant deposition difference reached one order of magnitude. The results suggest that a more accurate nasal cavity model is necessary in order to more precisely study the olfactory function of the nose when using the rat.     

Supine position decreases the ability of the nose to warm and humidify air.

We tested the hypothesis that decreasing nasal air volume (i.e., increasing nasal turbinate blood volume) improves nasal air conditioning. We performed a randomized, two-way crossover study on the conditioning capacity of the nose in six healthy subjects in the supine and upright position. Cold, dry air (CDA) was delivered to the nose via a nasal mask, and the temperature and humidity of air were measured before it entered and after it exited the nasal cavity. The total water gradient (TWG) across the nose was calculated and represents the nasal conditioning capacity. Nasal volume decreased significantly from baseline without changing the mucosal temperature when subjects were placed in the supine position (P < 0.01). TWG in supine position was significantly lower than that in upright position (P < 0.001). In the supine position, nasal mucosal temperature after CDA exposure was significantly lower than that in upright position (P < 0.01). Our data show that placing subjects in the supine position decreased the ability of the nose to condition CDA compared with the upright position, in contrast to our hypothesis.     

Acoustic rhinometry in dog and cat compared with a fluid-displacement method and magnetic resonance imaging.

An increasing number of studies have used acoustic rhinometry (AR) for study of pharmacological interventions on nasal cavity dimensions in dogs and cats, but there have been no attempts to validate AR in these species. This is done in the present study. We compared area-distance relationships of nasal cavities from five decapitated dogs (3.5-41 kg) and cats (3.8-6 kg). AR was compared with magnetic resonance (MR) imaging and a fluid-displacement method (FDM) using perfluorocarbon. AR measured 88% (98-79%) (mean and 95% confidence interval) of nasal cavity volume in dogs determined by FDM and 71% (83-59%) in cats. AR markedly underestimated nasal cavity dimensions when minimum areas were below 0.1 cm2 in dogs and 0.05 cm2 in cats. AR underestimation increased with the severity of the constriction and with distance. Cross-sectional areas in the deeper parts of the cavity measured 76% (99-54%) of FDM in dogs and 52% (66-39%) in cats. AR agreed well with MR, especially in the deeper part of the cavity. MR images showed that the nasal cavities had a very complex structure not expected to be reproduced by AR. MR could not be considered a "gold standard" because definition of the cross-sectional area of the lumen depended critically on subjective choices. FDM produced repeatable measurements and possibly offers the most adequate reference in future evaluation of AR. AR underestimated what we believed were the most correct cross-sectional areas determined by FDM, especially in the deeper part of the dog and cat nasal cavities. Despite these difficulties, AR has been shown to be useful to describe qualitative changes in cross-sectional area.     

Inspirational airflow patterns in deviated noses: a numerical study

This study attempts to evaluate the effects of deviation of external nose to nasal airflow patterns. Four typical subjects were chosen for model reconstruction based on computed tomography images of undeviated, S-shaped deviated, C-shaped deviated and slanted deviated noses. To study the hypothetical influence of deviation of external nasal wall on nasal airflow (without internal blockage), the collapsed region along the turbinate was artificially reopened in all the three cases with deviated noses. Computational fluid dynamics simulations were carried out in models of undeviated, original deviated and reopened nasal cavities at both flow rates of 167 and 500 ml/s. The shape of the anterior nasal roof was found to be collapsed on one side of the nasal airways in all the deviated noses. High wall shear stress region was found around the collapsed anterior nasal roof. The nasal resistances in cavities with deviated noses were considerably larger than healthy nasal cavity. Patterns of path-line distribution and wall shear stress distribution were similar between original deviated and reopened models. In conclusion, the deviation of an external nose is associated with the collapse of one anterior nasal roof. The crooked external nose induced a larger nasal resistance compared to the undeviated case, while the internal blockage of the airway along the turbinates further increased it.     

Mucosal targeting of a BoNT/A subunit vaccine adjuvanted with a mast cell activator enhances induction of BoNT/A neutralizing antibodies in rabbits

Background

We previously reported that the immunogenicity of Hcβtre, a botulinum neurotoxin A (BoNT/A) immunogen, was enhanced by fusion to an epithelial cell binding domain, Ad2F, when nasally delivered to mice with cholera toxin (CT). This study was performed to determine if Ad2F would enhance the nasal immunogenicity of Hcβtre in rabbits, an animal model with a nasal cavity anatomy similar to humans. Since CT is not safe for human use, we also tested the adjuvant activity of compound 48/80 (C48/80), a mast cell activating compound previously determined to safely exhibit nasal adjuvant activity in mice.

Methods

New Zealand White or Dutch Belted rabbits were nasally immunized with Hcβtre or Hcβtre-Ad2F alone or combined with CT or C48/80, and serum samples were tested for the presence of Hcβtre-specific binding (ELISA) or BoNT/A neutralizing antibodies.

Results

Hcβtre-Ad2F nasally administered with CT induced serum anti-Hcβtre IgG ELISA and BoNT/A neutralizing antibody titers greater than those induced by Hcβtre + CT. C48/80 provided significant nasal adjuvant activity and induced BoNT/A-neutralizing antibodies similar to those induced by CT.

Conclusions

Ad2F enhanced the nasal immunogenicity of Hcβtre, and the mast cell activator C48/80 was an effective adjuvant for nasal immunization in rabbits, an animal model with a nasal cavity anatomy similar to that in humans.     

The early development of the Jacobson's organ in the cat (Felis silvestris)

The histological study of the nose of an embryo of the cat (Felis silvestris 10 mm) presents a simple cavity which caudally communicates with the oral cavity by a narrow cleft, the primitive choana. This aperture results from the former rupture of the membrana bucconasalis of which the present material still contains remnants. Compared to the simple nasal cavity, the organ of Jacobson, situated at the base of the broad fetal nasal septum, shows a progressive development. From this one might conclude, according to ontogenetical rules, an early functional importance of the accessory olfactory organ. The currently fetal nose under investigation presents the organ as a primary open groove which increases in depth from rostral to caudal. Only caudally, a short section of the organ is already formed into a tube. From the functional point of view, the epithelial lining of this organ is still undifferentiated, but its dorsal part is clearly thickened. It seems that this indicates an early arrangement of the later olfactory epithelium. Beside this it is striking that in early fetal life, the organ of Jacobson extends to a remarkable length within the nasal cavity. Obviously the organ occupies, early in ontogeny, its area inside the little developed nose. Finally, the striking resemblance of the topography of the organ of Jacobson between early embryos of mammals and those of fetal and even some adult reptiles is discussed.     

Nasal cavity dimensions in guinea pig and rat measured by acoustic rhinometry and fluid-displacement method.

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 mm(3) (95-100 mm(3)) (mean and 95% confidence interval) of the first 2 cm of the cavity. FDM measured a mean volume of 146 mm(3) (117-175 mm(3)), meaning that AR only measured 70% (50-90) of the volume by FDM. For rats, the volume from 0 to 2 cm was 58 mm(3) (55-61 mm(3)) by AR and 73 mm(3) (60-87 mm(3)) 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.     

Effects of paranasal sinus ostia and volume on acoustic rhinometry measurements: a model study.

We used pipe models to investigate the effects of paranasal sinus ostium size and paranasal sinus volume on the area-distance curves derived by acoustic rhinometry (AR). Each model had a Helmholtz resonator or a short neck as a side branch that simulated the paranasal sinus and sinus ostium. The AR-derived cross-sectional areas posterior to the ostium were significantly overestimated. Sinus volume affected the AR measurements only when the sinus was connected via a relatively large ostium. The experimental area-distance curve posterior to the side branch showed pronounced oscillations in association with low-frequency acoustic resonances in this distal part of the pipe. The experimental results are discussed in terms of theoretically calculated "sound-power reflection coefficients" for the pipe models used. The results indicate that the effects of paranasal sinuses and low-frequency acoustic resonances in the posterior part of the nasal cavity are not accounted for in the current AR algorithms. AR does not provide reliable information about sinus ostium size, sinus volume, or cross-sectional area in the distal parts of nasal cavity.     

AQUATIC MATING STRATEGIES OF THE MALE PACIFIC HARBOR SEAL (PHOCA VITULINA RICHARDII): ARE MALES DEFENDING THE HOTSPOT?

Compared to the harem and resource defense systems of terrestrial mating pinnipeds, males of aquatic mating species appear unable to monopolize females or resources. We investigated movements, acoustics, and aquatic territorial behavior of male harbor seals, Phoca vitulina richardii , in Elkhorn Slough, California, using VHF telemetry, hydrophones, and acoustic playback experiments. During the mating season 22 males increased time spent in the water and away from haul-out locations, exhibiting activity patterns similar to Atlantic subspecies. Two acoustic display patterns were observed. At one location multiple males aggregated to display with acoustic activity peaking one month before peak estrus. At two other locations, lone males displayed primarily during peak estrus. Acoustic display areas were non-adjacent with a mean ± SE size of 4,228 ± 576 m², similar to harbor seal display patterns in the Moray Firth, Scotland. Underwater playbacks of male vocalizations were used to define territorial boundaries by inducing responses from territory-holding males. Four solitary males defended adjacent territories (mean area 39,571 ± 18,818 m²) along a travel corridor, similar to observations of harbor seals at Miquelon, Newfoundland. Acoustic display stations appeared to be subcomponents of larger territories. Males exhibited site fidelity to territories for at least 2–4 yr. Females moved through territories freely. The establishment of male-display territories along female-traffic corridors resembles terrestrial systems described as hotspot leks.