Modelling the nasal Cavity

When the velum is lowered during the production of nasals and nasalised vowels, sound enters via the velar gap, propagates through the nasal cavity and radiates through the nose. Hence for a more complete model, we have to add a component for the nasal cavity. This in itself is relatively straightforward to model for a start, it is a static articulator, so doesn t have anywhere near the complexity of shapes that occur in the oral cavity. By much the same techniques we employed above, we can construct an all-pole transfer function for the nasal cavity. 

Acoustically, the effect of the side branch is to trap some of the sound, and this creates anti-resonances. These can be modelled by the inclusion of zeros in the transfer function. As with the case of nasalised vowels, the parallel nature of the system means we can t use a single transfer function rather we have a system with an all-pole transfer function for the pharynx and back of the mouth, a splitting operation, an all-pole function for the nose and a pole and zero function for the oral cavity. 

Many consonant sounds, such as fricatives and stops, have a sound source located in the oral cavity. This is created by the tongne nearing another surface (tiie roof of the moufli. 

The effect of a sound source in the middle of the vocal tract is to split the source such that some sound travels backwards towards the glottis while the remainder travels forwards towards the lips. The vocal tract is thus effectively split into a backward and a forward cavity. The forward cavity acts a tube resonator, similarly to the case of vowels but with fewer poles because the cavity is considerably shorter. The backward cavity also acts as a further resonator. The backward-travelling source will be reflected by the changes in cross-sectional area in the back cavity and at the glottis, creating a forward-travelling wave that will pass through the constriction. Hence the back cavity has an important role in the determination of the eventual sound. This back cavity acts as a side resonator, just as with the oral cavity in the case of nasals. The effect is to trap sound and create anti-resonances. Hence the back cavity should be modelled with zeros as weU as poles in its transfer function. 

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During mastication, nonvolatile flavor molecules must move from within the food, through the saliva to the taste receptors on the tongue, and the inside of the mouth, whereas volatile flavor molecules must move from the food, through the saliva and into the gas phase, where they are carried to the aroma receptors in the nasal cavity. The two major factors that determine the rate at which these processes occur are the equilibrium partition coefficient (because this determines the initial flavor concentration gradients at the various boundaries) and the mass transfer coefficient (because this determines the speed at which the molecules move from one location to another). A variety of mathematical models have been developed to describe the release of flavor molecules from oil-in-water emulsions. 

Following the same surgical operation as in the in vivo model, the drug remaining in the nasal cavity can be recovered at a predetermined time and analyzed in this simple model. This method is useful for evaluating both the absorption and the degradation of peptides. 

In addition to small molecules, a number of protein therapeutic agents, such as neurotrophic factors27 and insulin,28 have been successfully delivered to the CNS using IN delivery in a variety of species. The therapeutic benefit of IN delivery of proteins has been demonstrated by Liu et al. in rat stroke models.29 Their studies demonstrated that insulin-like growth factor I (IGF-I) could be delivered to the brain directly from the nasal cavity, even though IGF-I did not cross the BBB efficiently by itself. As a consequence, IN IGF-I markedly reduced infarct volume and improved neurological function following focal cerebral ischemia. Research in... 

Pharmacokinetic models to describe, as a function of formaldehyde air concentration, the rate of formation of formaldehyde-induced DNA-protein cross links in different regions of the nasal cavity have been developed for rats and monkeys (Casanova et al. 1991 Heck and Casanova 1994). Rates of formation of DNA-protein cross links have been used as a dose surrogate for formaldehyde tissue concentrations in extrapolating exposure-response relationships for nasal tumors in rats to estimate cancer risks for humans (EPA 1991a see Section 2. 4.3). The models assume that rates of cross link formation are proportional to tissue concentration of formaldehyde and include saturable and nonsaturable elimination pathways, and that regional and species differences in cross link formation are primarily dependent on anatomical parameters (e g., minute volume and quantity of nasal mucosa) rather than biochemical parameters. The models were developed with data from studies in which... 

It is important to note that the rabies virus can also be transmitted through the colonization of the olfactory bulbs via the nasal cavity (Fig. 12.4). Indeed, animal models of infection have shown that viruses could migrate from the olfactory bulb to higher brain regions, including the basal nuclei, hypothalamus, and cerebellum. " ... 

The human oral cavity is potentially coimected to the nasal cavity by way of the buccopharynx (oropharynx), pharynx, and nasopharynx [1,2]. Under those circumstances in which this potential connection is open, the air movement of an exhalation that exits from the anterior nates (nostrils) can acquire odorants from the oral cavity and move them through the nasal cavity. If these odorants, while in the nasal cavity, reach the olfactory mucosa at a flow rate and concentration [3,4] that allow penetration to olfactory receptor neurons [5] and activation of these receptors such that sufficient central nervous system (CNS) responses develop, retronasal olfaction may occur. A limitation to the present understanding of retronasal olfaction is the absence of empirical or numerical models of retronasal odorant transport in adult humans. Such models have been published for orthonasal olfaction via the anterior nares [4,6] but are not presently available for retronasal olfaction (experimental airflow and odorant uptake analysis is in progress PW Scherer, personal communication, October 2002). 

Identical olfactory neurons are located in different places in the cavity, and therefore occupy different positions in the flow path. By using a nasal cavity model, we investigated the influence of the dynamic flow on the sensors response14. The responses from identical fiber optic sensors located... 

Figure 9. A plastic model of a nasal cavity showing the different positions (numbers 1-5) of the sensors. Reprinted with permission from ref. 14. Copyright 2003 American Chemical Society.

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