Flow Measurements in Patient Specific Conducting Airways Models:
Towards Tailoring Treatment of Asthma and COPD
http://www.airprom.european-lung-foundation.org/
http://www.airprom.eu
B. Timmerman, G. Gibbons and P.J. Bryanston-Cross
AirPROM
In Silico Modelling
The EU-funded programme AirPROM aims to develop models of human airways to
assess how air flows through the lungs and why this flow becomes obstructed in
people with asthma and Chronic Obstructive Pulmonary Disease (COPD). This will
enable development and testing of new individually tailored therapies, through linking
the characteristics of different airways to a particular treatment. Furthermore this will
aid monitoring future risks to patients by helping predictions regarding the effect on
the airways and the progression of the diseases. As part of this project techniques are
developed to study flows in human conducting airways to improve understanding of
underlying mechanisms in asthma and COPD. Realistic in silico airway models are
created through additive layer manufacturing of segmented lung CT scans. Flow
measurements are obtained in these models using (high-speed) particle image
velocimetry (PIV). This enables study of breathing dynamics, which will allow
validation and development of CFD models and in vivo MRI velocimetry.
To understand how lung-conditions affect patients’ breathing, patient-specific in silico
models of the conducting airways are created, which allow the airflow in lungs to be
studied. For this, a patient’s CT data is segmented to extract the 3-dimensional shape of
the airways. A model is then created of these airways using Additive Layer
Manufacturing (ALM) techniques.
Optically Transparent Models
Two types of optically transparent RP models of conducting human airways have been
created.
Low order model
Segmented CT: lower airways
Segmented airway data was clipped down to 2nd order. This was used to
produce a rapid-prototyped model constructed from water soluble support
material (SR-30). After smoothing RP-layer surface imperfections the model was
encapsulated by urethane rubber (Clear Flex® 50 water clear, Smooth-On Inc)
with an estimated Young's modulus of ~2.47MPa, similar to that of the trachea
and bronchial tubes. The core was then dissolved using an alkaline detergent
(P400SC), leaving an optically transparent rectangular block with hollow
passages in the shape of the airways.
High order transparent model
High order model
To enable study of the effects of complex airway geometry a 7th order CT-based
rigid transparent model was produced through standard RP.
Compliant models
Methodologies will be developed for the use of ALM techniques to provide flexible
compliant boundary high-order airway physical models with an anatomically and
mechanically-realistic description of the airway, based on bronchial tube tissue (muscle
and cartilage) mechanical properties. This will make use of novel multi-material ALM
technology (Objet Connex 260).
Asthma: Patients suffering asthma have inflamed airways,
making them swollen and very sensitive. When the airways
react, mucus production increases and the muscles around
airways tighten, narrowing them and thus causing less air
to flow into the lungs. http://www.nhlbi.nih.gov
Lung CT data. http://www.rad-zep.de
COPD: COPD typically involves two separate lung conditions: chronic bronchitis and emphysema.
In chronic bronchitis, the airways (bronchi) become inflamed, congested with mucus, and
narrowed, resulting in obstructed air flow. In emphysema, the walls of the air sacs (alveoli) are
destroyed, leading to fewer but larger alveoli, making them less efficient in transferring oxygen
from the lungs to the bloodstream.
High order model PIV: raw image, instantaneous and average 2C velocity
Outlook
Low order transparent model
with RP core
- High-speed PIV will be used to capture real time response of air flow to boundary movement,
both on global large-scale as well as localised high-resolution, providing insight into ventilation
dynamics and airflow mechanisms in human lungs in obstructive airway diseases. The
integration of the large scale analysis with the local scale analysis will allow small scale effects on
flow (e.g. reduced air flow due to partial closure of the middle lobar bronchus) to be correlated
to an overall large-scale change in flow pattern (e.g. flow field in the trachea), thus providing a
true macro-large airway CFD validation.
Asthma and COPD
Asthma and COPD are wide-spread, serious health problems with asthma affecting
300 million people, while 80 million people have moderate–to–severe COPD
worldwide. They impose serious health risks with asthma estimated to cause
approximately 239,000 deaths worldwide per year and COPD predicted to be the 3rd
leading cause of death in the world by 2030 [1]. In people with COPD and asthma
damaged, inflamed or obstructed airways are common, hindering breathing. Current
methods to detect and treat these conditions do not consider individual differences
between airways and although targeted approaches to treatment are being
developed, often it has been unknown how to match these to specific patients. Thus,
people suffering from these conditions may not get the optimal treatment.
- Methods will be developed to obtain measurements for compliant opaque models, including
endoscopic PIV, X-ray PIV [5] and digital holography [6].
- The in silico prototypes will be used for validation of ultrafast hyperpolarised 3He MRI, which
has been shown to provide insight into in vivo ventilation dynamics in human lungs [7].
- With flow phantoms of known geometry and input flow rates and pressures that can be
controlled, a direct means of validation of CFD calculations with well-defined experimental
boundary conditions is provided.
Low order model: 2C velocity
Low order model: 3C velocity
Airways tissue
Segmented CT: lower and upper airways
Particle Image Velocimetry
References
[1] AirPROM consortium website, http://www.airprom.european-lung-foundation.org or http://www.airprom.eu
Illuminated model with dissolved core and diagram for PIV system
Flows in human airways have been studied using CT-based silicone optically transparent rapid
prototyped models with a water-glycerine mixture as the refractive index matched working fluid,
generally aimed at improving artificial ventilation (e.g. [2]-[4]). In the experiments described here
these techniques are investigated further using particle image velocimetry (PIV) to study the flow
dynamics, based on patient specific breathing patterns. To minimise distortions due to refractive index
differences here rapeseed oil is used as flow medium, enabling visualisation in the complex airway
geometries. To enable velocity measurements the flow is seeded with reflective polyamide particles of
50 µm diameter. A light sheet is used to illuminate a plane or thin volume in the geometry. The
movement of the particles is then recorded using a (high-speed) camera and velocities are extracted.
By scanning the light sheet different parts of the airways can be investigated and the turbulent flow
distribution through the complete airway geometry can be built up.
[2] M. Vermeulen, C. van Holsbeke, T. Claessens, J. de Backer, P. van Ransbeeck, P. Verdonck, “Flow Analysis in Patient Specific Lower Airways using
PIV", 15th Int Symp on Applications of Laser Techniques to Fluid Mechanics, Lisbon, Portugal, 05-08 July; 2010.
[3] T. Soodt, F. Schröder, M. Klaas, T. van Overbrüggen and W. Schröder, “Experimental investigation of the transitional bronchial velocity distribution
using stereo scanning PIV”, Experiments in Fluids, Online First 4May 2011.
[4] S. Große, W. Schröder and M. Klaas, “Time-Resolved PIV Measurements of Vortical Structures in the Upper Human Airways”, Topics in Applied
Physics, vol. 112,, pp. 35-53, 2008
[5] S. Dubsky, S.B. Hooper, K.K.W. Siu, A. Fouras, “Dynamic four-dimensional X-ray PIV of the lung”, 9th International Symposium on Particle Image
Velocimetry –PIV’11, Kobe, Japan, July 21-23, 2011.
[6] D. Claus, M. Fritzsche, D. Iliescu, B. Timmerman, and P. Bryanston-Cross, "High-resolution digital holography utilized by the subpixel sampling
method", Applied Optics, Vol. 50, Issue 24, pp. 4711-4719, 2011
[7] J.M. Wild, M.N.J. Paley, L. Kasuboski, A. Swift, S.Fichele, N. Woodhouse, P.D. Griffiths, E.J.R. van Beek, “Dynamic radial projection MRI of inhaled
hyperpolarized 3He gas”, Magn Reson Med 49:991–997, 2003
Acknowledgements: Olympus KeyMed Ltd., P. Hackett, C. Maske, A. Patronis, T. Bradbury, S. Final, D. Carter
WMG/OEL School of Engineering, University of Warwick, Coventry, UK
B.H.Timmerman@warwick.ac.uk, G.J.Gibbons@warwick.ac.uk, P.J.Bryanston-Cross@warwick.ac.uk