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 OUTLOOK AirPROM - Compliant high-order airway models are produced which are anatomically and mechanically realistic using locally varying material properties 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 ADDITIVE LAYER MANUFACTURING 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 assembled. 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. PARTICLE IMAGE VELOCIMETRY DISCUSSION 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 modifications. 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 provided. 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]. REFERENCES 1. 2. www.airprom.eu M. Vermeulen, C. van Holsbeke, T. Claessens, J. de Backer, P. van Ransbeeck, P. Verdonck,15th Int Symp on Applications of Laser Techniques to Fluid Mechanics, Lisbon, Portugal, 05-08 Jul. (2010) 3. T. Soodt, F. Schröder, M. Klaas, T. van Overbrüggen, W. Schröder, Exp. Fluids 52(3) (2011) pp. 709-718 4. T. Soodt, D. Pott, M. Klass, W. Schröder,16th Int Symp on Applications of Laser Techniques to Fluid Mechanics, Lisbon, Portugal, 0912 July, 2012 5. B. Timmerman, G. Gibbons, P. Bryanston-Cross, 16th Int Symp on Applications of Laser Techniques to Fluid Mechanics, Lisbon, Portugal, 09-12 July, 2012 6. B. Timmerman, G. Gibbons, P. Bryanston-Cross,10th Int. Symp. On Particle Image Velocimetry PIV’13, Delft, The Netherlands, 01-03 July 2013 7. C. van Ertbruggen, C. Hirsch, M. Paiva, J Appl Physiol 98 (2005) pp. 970–980 8. S. Dubsky, S.B. Hooper, K.K.W. Siu, A. Fouras, 9th International Symposium on Particle Image Velocimetry –PIV’11, Kobe, Japan, July 21-23, 2011. 9. D. Claus, M. Fritzsche, D. Iliescu, B. Timmerman, and P. Bryanston-Cross, Applied Optics, Vol. 50, Issue 24, pp. 4711-4719, 2011 10. J.M. Wild, M.N.J. Paley, L. Kasuboski, A. Swift, S.Fichele, N. Woodhouse, P.D. Griffiths, E.J.R. van Beek, Magn Reson Med 49:991– 997, 2003 11. D.M.L. Lilburn, G.E. Pavlovskaya, T. Meersmann, J Magn Reson. 229(C) (2013) pp. 173–186. 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 B.H.Timmerman@warwick.ac.uk, WMG, University of Warwick, Coventry CV4 7AL, UK