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How reliable is the extrapolation? Localized


particle deposition patterns in human/rat nasal
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ARTICLE JANUARY 2016

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Yidan Shang

Jingliang Dong

RMIT University

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Retrieved on: 30 January 2016

Proceedings of the ASME 2015 International Mechanical Engineering Congress & Exposition
2015 IMECE
November 13-19, 2015, Houston, Texas, USA

IMECE2015-52494
HOW RELIABLE IS THE EXTRAPOLATION? LOCALIZED PARTICLE DEPOSITION
PATTERNS IN HUMAN/RAT NASAL CAVITIES
Yidan SHANG, Jingliang DONG, Kiao INTHAVONG, Jiyuan TU*
School of Aerospace, Mechanical & Manufacturing Engineering of RMIT and Platform Technologies
Research Institute (PTRI).
PO Box 71, Bundoora, VIC 3083, Australia.

ABSTRACT
To improve the understanding of dose-response
extrapolation from rat to human, regional micro-particle
deposition patterns are numerically investigated and compared
between human and rat realistic nasal cavities using
Computational Fluid Dynamics (CFD). Resting breathing
conditions are chosen and airflow patterns are visualised by
streamlines. To have better comparisons of deposition patterns,
deposited particles are projected into pre-divided 2D domains
based on anatomical features using surface-mapping technique.
The results show significant differences between human and rat
due to the different nasal geometries, especially at vestibule
regions. In human case, large micro-particles deposit primarily
in vestibule, septum and pharynx and small micro-particles
relatively scattered in the whole cavity. On the contrary, in the
rat case, large and small micro-particles are captured by the first
and second bend of vestibule region.
INTRODUCTION
The nasal cavity is an efficient filtering component of upper
respiratory tract to protect the lung from airborne particles. To
evaluate the health risk by inhalation exposure, toxicity data
extrapolation from laboratory animals (e.g. rat, monkey) to
humans is widely used. Previous in-vivo and in-vitro
experimental studies indicated the nasal filtering is efficient when
micro-sized particles larger than 10 m (for human) or 5 m
(for rat), and nano-sized particles smaller than 10 nm (both for
human and rat) [1-6]. Micro-particle deposition efficiency
increases rapidly as inertial increases with the size.
Experiments are costly and inefficient in this type of
investigations. Particle dosimetry models such as MPPD model
[7, 8] and semi-empirical model [9] have been developed to
predict the deposition efficiencies of inhaled particles among
different regions of the respiratory system for human and rat.
Computational fluid dynamics (CFD) simulation is an alternate

way to estimate airflow patterns and main particle deposition


sites. Due to the intricate nasal cavity geometry, majority of
previous studies focused their research efforts on overall particle
deposition analysis. Numerous numerical studies roughly
indicated that the deposited micro-sized particles are mainly
concentrated at the nasal valve and the septum for the human
model, and at the anterior region of the nose for rat [10-13].
Besides, regional particle deposition efficiencies in the nasal
cavity are important as particles can cross the respiratory
epithelium and reach the underlying tissue, blood vessels and
even brain via the Blood-Brain-Barrier [14]. However to date,
comparative studies of particle deposition patterns between
human and rat nasal cavities are limited because visualization of
deposition patterns are difficult even with a 3D viewer due to
the complexity of highly curved nasal geometries.
In this paper, airflow patterns and micro-particle deposition
patterns are investigated and compared between human and rat
nasal cavities. To advance the analysis method of particle
deposition, particle deposition patterns are visualized by surface
mapping technique proposed by Inthavong et al. [15-17]
converting the complex 3D endothelial surface of nasal cavity
into a flat 2D domain. Both human and rat nasal cavities are
anatomically divided into seven regions accordingly for
analysing and comparing regional depositions. This comparative
study can contribute towards improving extrapolations of
physiological response to inhaled particles from rat to human.
METHOD
A. Geometry
Two realistic models representing human (labeled as NC04,
48-year-old male) and rat (labeled as RNC01, 400g SpragueDawley) nasal cavities are reconstructed from CT scans (Fig
1a,1b), the detailed reconstruction method of which can be
found in [18]. Each model includes both left and right nasal

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chambers, olfactory region, pharynx and larynx. Besides,


external spaces are created outside nasal cavities together with
detailed facial features. Different from using uniform boundary
condition at nostrils, adding this external space guarantees
realistic injection conditions as they are significantly influenced
by the airflow in the breathing region [16]. The size of nasal
cavity of rats is about one third of that of humans, while the
surface features of rats are significantly more complex than
those of humans, especially in the olfactory region, leading to
much larger surface area, different flow patterns and particle
deposition distributions.

accelerating stage and the injection locations are usually biased


due to the inertial.
C. Surface mapping technique
Each nasal model is divided into seven regions (vestibule,
olfactory, pharynx, septum and upper/middle/lower passages)
for localised particle deposition analysis (Fig 1c,1d). The only
difference is that the maxillary sinuses (colored in pink) are
retained in rat model as they contribute slight effects on airflow
patterns. Each divided nasal surface is projected into the 2D
domain using surface mapping technique by cutting along the
bottom and then normalized into two rectangles without
breaking regions connectivity. The additional horizontal straight
lines separate each cavity into lateral part and septal part, and
two additional vertical straight lines separate each cavity into I
(vestibule), II (main passage) and III (pharynx). Mapped images
are further normalized to have direct comparisons between two
species. More details of mapping technique can be found in our
previous papers [16, 17].
RESULTS
A. Inhalation airflow patterns

Figure 1. Nasal geometries and mapping strategies for human


(NC04) and rat (RNC01) models. (a,b) Respiratory airway
passages (green) extracted from CT-scans. (c,d) 3D models of
human and rat nasal cavities and their partitioning strategy. (e,f)
Mapped nasal surfaces in the 2D domain.
B. Numerical settings
Ansys-Fluent is used to simulate the airflow and trace
particles trajectory under steady relaxing breathing conditions
(15 L/min for human [9] and 0.4 L/min for rat [19]) using mesh
with sizes of nearly 5 million for both species. Laminar flow is
chosen because negligible turbulence was found in previous
studies under relaxing conditions. Zero-pressure condition and
velocity outlet are applied respectively at the external
boundaries and the outlet of the fluid domain which is located at
larynx. Micro-sized particles are driven by air drag force and
gravity force. Particles are released uniformly from the external
space with zero initial velocity to guarantee a reasonable and
realistic injection through nostrils as they experience an

Figure 2. Airflow streamlines are visualised to reveal flow


patterns inside the nasal cavities of human(a) and Rat(b). Two
representative streamlines are colored by velocity magnitude
showing nasal airflow motions for human(c) and rat(d).
Streamlines traced from the external space are plotted
together with the nasal geometry to illustrate the likely paths
particles may follow. For the human model, air preferentially
flows through the middle and lower passage leaving negligible
swirling flow near the olfactory region and the upper passage
(Fig 2a). Air steadily accelerates to 4 m/s when inhaled into

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nostrils and decelerates slightly till it reaches the pharynx region,


and then accelerates again to 6.5 m/s (Fig 2c). While in rats
case the airflow immediately turns sharply followed by a 180
degree bend and a 90 degree bend when inhaled into nostrils,
drastically accelerating it from nearly 0 to 10 m/s (Fig 2d). This
leads to significant impact of high inertial particles. The air
predominantly flows through the middle passage and a large
recirculation is found in the pocket-like olfactory region (Fig
2b), which may provide a possible site for particle deposition.

especially for large particles (100% deposition) as shown in the


enlarged view. This is due to the unique nasal shape of two
sharp bends with 180 degree for the first bend and 90 degree for
the other one(Fig 2d). Small portion of small particles escaped
from vestibule are scattered in the main passage.
For both cases, particle deposition efficiencies for small
particles are below 5% while for large particles are nearly 100%.
However, further detailed deposition features could not be
revealed from here due to data overlapping.

B. 3D micro-particle deposition patterns


Ten thousand particles are visualised in lateral view by dots
in the 3D domain. The particle Stokes number (Stk) was used to
determine appropriate particles sizes representing equivalent
particle behavior between these two species. The particle
deposition efficiency is defined as the quantity of deposited
particles over inhaled particles.

C. 2D micro-particle deposition patterns

Figure 4. 2D view of micro-sized particles deposition of two


particular particle sizes representing Stk < 0.1 and Stk > 1 in
human (a), and rat (b).

Figure 3. 3D view of micro-sized particles deposition of two


particular particle sizes representing Stk < 0.1 and Stk > 1 in
human (a), and rat (b).
Figure 3 illustrates deposition of small particles (Stk < 0.1,
2.5 m for human, 1 m for rat, and coloured by blue) and large
particles (Stk > 1, 20 m for human, 3 m for rat, and coloured
by red). In the human case, major deposition sites for large
particles are concentrated at the top of the vestibule, the main
passage and pharynx region (Fig 3a). While small particles
relatively scattered in the whole cavity. These patterns are
consistent with previous reported conclusions [10].
Comparing to the human model, the vestibule region of the
rat model performs more significant filtration function as the
majority of the inhaled particles deposits in this region,

Through converting the particle deposition patterns into 2D


views, more deposition features can be observed. According to
the human case in the Figure 4a, more particles deposit in the
right nasal cavity due to the asymmetric geometry. Besides, the
septum region captures almost all large particles which deposit
in the main passage. For the rat case (Figure 4b), large particles
are significantly concentrated at the top of the first bend in the
vestibule. As a supplement to the deposition patterns in the 3D
view, majority of small particles deposit in both bends in the rat
vestibule. Considerable portions of the remaining particles which
are scattered in the main passage mainly deposit in the olfactory
region.
CONCLUSION
To improve the data extrapolation from monitored
exposures of laboratory animals to possible human exposure

Copyright 2015 by ASME

scenarios, this study numerically compared micro- and nanosized particle deposition patterns in human and rat nasal cavities.
Simulations are based on realistic 3D models
reconstructed from CT scans. Differences of nasal size, shape
and structure between two species lead to different airflow
patterns and affect particle motions. The major anatomical
difference is found at the vestibule region, where two sharp
turns (a U-turn 180 degree bend followed by a 90 degree bend)
in the rat vestibule perform significant filtering functions
primarily for micro-particles. Deposited particles are visualized
in both 3D view and 2D view by applying the surface mapping
technique. Significant discrepancies of micro- and nano-particle
deposition patterns between the human and rat cases are
observed.
This study indicates that the extrapolation from laboratory
animals to human should be carefully considered due to their
physiological differences in the anatomical level. It also provides
an approach towards interspecies dose-response comparisons,
and facilitates policy makers and governments to conduct
particulate matter risk assessment and outline policies for
reducing emissions of certain particulates when necessary.
ACKNOWLEDGMENTS
This work was supported by the Australian Research
Council (ARC project ID DP120103958), and National Natural
Science Foundation of China (NSFC 21277080).
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*Correspondence email: jiyuan.tu@rmit.edu.au

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