Additive layer manufacturing (3D printing) of physiologically realistic

Additive layer manufacturing (3D printing) of physiologically realistic
patient specific airway models for study of flow modifications in asthma and COPD
B. Timmerman, G. Gibbons, P.J. Bryanston-Cross
- Compliant high-order airway models are produced which are
anatomically and mechanically realistic using locally varying material
The EU-funded programme AirPROM ("Airway Disease PRedicting Outcomes through Patient Specific
Computational Modelling”) [1] aims to advance new individually tailored therapies for asthma and
Chronic Obstructive Pulmonary Disease (COPD). As part of this project the work presented here is
focused on enabling investigation of typical airway and flow modifications seen in these diseases to
improve understanding of the underlying mechanisms.
For this novel multi-material additive layer manufacturing (ALM) techniques are developed to create
patient-specific airway models that are realistic in both anatomy (geometry) and mechanical behaviour
(compliance). Thus effects of changes in airway geometry and physiology that are characteristic of
asthma and COPD can be investigated in isolation as well as collectively, which is not possible in vivo.
Measurements of the flow dynamics in these anatomical models are obtained using advanced (highspeed) particle image velocimetry (PIV). Results are used for validation and development of
computational fluid dynamics (CFD) models and in vivo MRI velocimetry.
 Increasing compliance for higher order branches
 Multiple structures to represent e.g. cartilage or muscle tissue
 Multi-layered walls to simulate different tissue composition
Particle image velocimetry (PIV) is used to study the flow inside the airway models. To enable velocity
measurements the flow is seeded with small (typically 50 µm diameter or less), reflective particles. The
particles are neutrally buoyant in the flow medium, and will trace the flow behaviour. A light sheet is used
to illuminate a plane or thin volume in the geometry. Typically the light sheet is generated using a laser to
create short light pulses allowing the particle motion to be ‘frozen’ in the image. The movement of the
particles is then recorded using a (high-speed) camera and velocities are extracted based on the particle
displacement between two subsequent images. 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
To enable viewing the particle movement inside the complex airway geometries of the ALM models and to
minimise distortion in the images acquired, the refractive index of the model material and the fluid
medium need to be matched. Depending on the model material this may typically be achieved through
use of oil or water-glycerine mixtures (e.g. [2]-[6]).
The measurements presented here are obtained using a combination of synchronised digital cameras,
both standard double-exposure PIV and high-speed. Thus, stereo PIV can be performed, providing 3component velocity data, as well as volumetric PIV. The use of high-speed cameras allows time-resolved
measurements to be obtained to enable study of the flow dynamics.
Using time-resolved stereoscopic particle image velocimetry flow characteristics are measured at
different sections through the models identifying e.g. recirculation zones or uneven flow distribution (e.g.
from trachea to bronchi).
- ALM models are being used to simulate Forced Oscillation Technique
measurements using models of the airways and pharynx/larynx.
- Techniques are being developed for optical stress measurements to
enable wall stresses to be measured during flow cycles.
- High-speed PIV will be used to capture real time response of air flow to
wall movement, both on global large-scale as well as localised highresolution, 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 largescale change in flow pattern (e.g. flow field in the trachea), thus providing
a true macro-large airway CFD validation.
Furthermore, measurements were obtained in different planes of the ALM models,
showing the flow distribution through the various airway branches. Time-resolved
measurements show highly three-dimensional flow in higher order branches, illustrating
the importance of non-fully developed flows in the bronchioles due to their relatively short
lengths This confirms results previously reported for numerical simulations [7].
A number of hollow, optically transparent models of normal and asthmatic
conducting human airways have been created, as well as two generic
models representing basic airway geometry.
Measurements were obtained for first and second order geometric models, indicating
recirculation regions near the trachea-bronchi transition. A good correspondence is found
to CFD results.
To understand how lung-conditions affect patients’ breathing, patientspecific models of the conducting airways are created using Additive Layer
Manufacturing (ALM) techniques (3D printing). For this, a patient’s CT data
is segmented to extract the 3-dimensional shape of the airways from which
physical models are then created. Using multi-material ALM different
compliances can be mimicked in one model, enabling e.g. wall dynamics
and the effects of differing airway composition (muscle, soft tissue) and
corresponding flow dynamics to be investigated.
Geometric Models
Two types of geometric models have been created for initial comparison to
Computational Fluid Dynamics (CFD)
 First order
 Second order
This allows independent investigation of characteristic changes in airway
geometry and physiology to establish those responsible for flow
Multi-material tube under stress testing
Flows in lungs have been studied extensively over the past decade, both numerically and
experimentally. Most of these studies are of generic geometries. However, one of the most
important factors influencing the flow field is the geometry of the lung airways.
Furthermore, airway deformation needs to be taken into account for realistic flow patterns,
as the airways are compliant and will deform over the breathing cycle. The dynamics and
effect of this airway deformation is currently unknown, as typically CT scans are only
captured for full expiration and inspiration, whilst MRI currently lacks resolution for airway
segmentation. The present ALM models allow investigation of these effects.
- Methods under development for compliant opaque models include
endoscopic PIV, X-ray PIV [8] and digital holography [9].
Airways: multi-material structures
-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
CT-based Models
 Rigid models
To enable study of the effects of complex airway geometry a 7th order CTbased rigid transparent model was produced through standard stereo
lithography (SLA).
 Compliant models
Models have been created with flexibility similar to that of tracheal tissue
 Larynx
Creation of realistic inflow conditions
 Conducting airways
Low order models
- The ALM models 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 [10,11].
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Acknowledgements: The research leading to these results has received funding from the European Union Seventh Framework Programme
FP7/2007-2013 under grant agreement n° 270194. Further thanks to Olympus KeyMed Ltd., P. Hackett and AirPROM partners, WMG, University of Warwick, Coventry CV4 7AL, UK