optimality of the length-to-diameter ratio in the human bronchial tree

1
$598 Journal of Biomechanics 2006, Vol. 39 (Suppl 1) 7735 We-Th, no. 23 (P64) Optimality of the length-to-diameter ratio in the human bronchial tree E. Lee 1, M.'~ Kang 2, H.-J. Yang 2, J.W. Lee 2. 1City health Center, Pohang, Korea, 2Department of Mechanical Engineering and also Systems Bio-Dynamics Research Center, Pohang University of Science and Technology, Pohang, Korea Human bronchial tree has a very complex structure, and the geometric param- eters such as diameter, length and branching angle differ from generation to generation. Of various geometric parameters defining the bronchial structure, the diameter ratio and branching angle at branching has been found to result from an optimality rule, minimizing the pressure loss under a volume constraint condition. This paper extends the optimality rule to show that the nearly constant length-to-diameter ratio observed with conducting airways of human bronchial tree is the result of fluid dynamic optimality. In any branched tube there are two pressure loss mechanisms, one for wall friction in the tube section and the other for flow division in the branching section, and there exists an optimal length-to-diameter ratio which minimizes the total pressure loss for a branched tube in laminar flow condition. The optimal length-to-diameter ratio predicted by the pressure loss minimization shows an excellent agreement with the length-to-diameter ratios found in the human conducting airways. 7779 We-Th, no. 24 (P64) Intravital endo-microscopy of alveoli: a new method to visualize alveolar dynamics C.A. Stahl 1, S. Schumann 1, H. Knorpp 1, M. Schneider 1, K. MSIler2, J. Guttmann 1. 1Department of Anesthesiology and Critical Care Medicine, University of Freiburg, Germany, 2Biomedical Engineering, Furtwangen University, Germany Introduction: In the frame of protective lung ventilation the alveolar biome- chanics come more and more in the focus of the scientific interest. New microscopic techniques and experimental setups enable a view on the alveoli dynamically changing their geometry under mechanical ventilation [Schiller et al. (2003) CCM 31(4)]. Although of fascinating image quality the alveoli are observed at an open chest wall under a glass plate representing an artificial situation. To circumvent this restriction we developed a method of intravital endo-microscopy and tested it on an animal model (rat). Methods: In cooperation with Schoelly GmbH (Denzlingen, Germany) we developed a rigid endo-microscope. The endoscope tube can be introduced vertically into the thorax by minimally invasive thoracostomy. The system is being placed in the plane of the pleura thus enabling microscopy of in- vivo alveolar dynamics without mechanical deformation of the alveoli under observation. The space between the lens and the lung tissue is flushed with clear fluid. Excess fluid is evacuated through an outer trocar. By applying a few cmH20 of negative pressure to the outer trocar, the lung surface is kept in contact with the inner chest wall. Results: The new optical system provides excellent image quality of subpleural alveoli in the closed chest. The construction of the system and simultaneously acquired video-sequences of microscopic data and PV analyses will be pre- sented. Conclusion: This new minimal invasive method of intravital endo-microscopy enables the observation of the dynamic behaviour of alveoli in the closed chest in situ. The concurrent observation of respiratory mechanics and alveolar dynamics provides a promising tool to correlate global analysis of respiratory mechanics with local alveolar properties. 7022 We-Th, no. 25 (P64) Airway reopening: oscillating air finger propagation through a liquid-filled tube B.J. Smith, D.P. Gaver II1. Tulane University, New Orleans, USA Acute respiratory distress syndrome (ARDS) is characterized by pulmonary airway collapse and fluid occlusion. Subsequent airway reopening, driven by mechanical ventilation, generates damaging stresses and stress gradients on the airway walls. Through our ongoing research we strive for a thorough understanding of the mechanics of this process, yielding ventilation strate- gies that reduce or eliminate airway epithelial trauma. In the present study we computationally investigate the unsteady propagation of a finger of air through a liquid-filled rigid tube. The system, a free surface with fluid-structure interaction, is modeled using the boundary element method (BEM) coupled to lubrication theory in the upstream thin film region. An axisymmetric model is posed, which consists of a BEM region spanning from the downstream end to a point on the air-liquid interface where small slope assumptions hold. Further upstream, lubrication theory is used to resolve the thin film. The system is governed by three dimensionless parameters: the capillary number Ca = ~tU/y, consisting of mean (Ca M) and sinusoidal oscillatory (Ca~2) compo- nents, represents the balance between viscosity (~t), velocity (U), and surface tension (y). The dimensionless frequency ~2 = ~t(,)R/y and amplitude A = 2Ca~/~2 Poster Presentations parameterize bubble oscillation. Converging and diverging stagnation points are important for determining the location of surfactant accumulation and deposition, respectively. We find that these stagnation points move dynamically throughout the cycle; typically occurring on the interface at low ~2, these points separate into the bulk of the fluid as ~2 increases. Cycle averaged results show that for increasing ~2 bubble tip velocity increases while residual film thickness decreases accordingly. Cycle-spatial averaging demonstrates an increasing influence of viscous forces on the pressure drop at the bubble tip as ~2 increases, particularly for high amplitude cases. Supported by NASA grant NAG3-2734 and NIH P20-EB001432 4700 We-Th, no. 26 (P64) Direct maximum expiratory flow modeling from lung function testing of pediatric patients J. Sznitman 1, B. Spycher 2, U. Frey 3, J.H. Wildhaber 4. 1Institute efFluid Dynamics, ETH Zurich, Switzerland, 2Department of Social and Preventive Medicine, University of Berne, Switzerland, 3pediatric Respiratory Medicine, Department of Pediatrics, University Hospital of Berne, Switzerland, 4Division of Respiratory Medicine, University Children's Hospital Zurich, Switzerland Since their introduction [1], maximal expiratory flow-volume (MEFV) curves have become a widely used non-invasive lung function test, potentially sensi- tive to respiratory mechanics and obstruction. In asthma, spirometry is consid- ered the standard tool for objective assessment, and lung function parameters, in particular FEV1 (forced exhaled volume in 1 s), are used not only in the assessment of disease severity but also as the primary outcome in clinical studies [2]. However, most asthmatic children have lung function values in the normal range independent of disease severity [3]. Such parameters generally reflect single data points extracted from flow-volume (FV) curves, making their efficacy and interpretation somewhat limited. In the present investigation, we show that rather than using classic lung function parameters, the behavior of FV curves may be better understood based on mathematical differentiation schemes and in particular the definition of convexity. Similar to the concept of slope ratio (SR) based on instantaneous tangent slopes of the FV curve [4], the behavior of the second derivative of the FV curve leads to suitable models describing the configuration of pediatric patient FV curves. In a further step, we show that the definition of a local and average curvature of FV curves may be directly related to expiratory volume acceleration and furthermore used as an index to characterize flow obstruction in asthmatic patients. In the near future, such models may be directly incorporated into spirometric hardware and used in lung function diagnostic. References [1] Hyatt R.E., et al. J. Appl. Physiol. 1958; 13: 331-336. [2] Bacharier L.B., et al. J. Allergy Clin. Immunol. 2002; 109: 266. [3] Verini M., et al. Allergy Asthma Proc. 2001; 22: 297-302. [4] Mead J. J. Appl. Physiol. 1978; 44: 156-165. 7354 We-Th, no. 27 (P64) Lung tissue mechanics after bleomycin-induced lung injury: Inflammation vs fibrosis M. Pinart 4, A. Serrano 2, E.M. Negri 3, R. Cabrera 1, P.R.M. Rocco 4, P.V. Romero 1. 1Laboratory of Experimental Pneumology, IDIBELL, L'Hospitalet, Barcelona, Spain, 2Department of Experimental Pathology, IIBB-CSIC, IDIBAPS, Barcelona, Spain, 3Department of Pathology, Clinical Hospital, University of Sao Paule, Sao Paule, Brazil, 4Laboratory of Respiration Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Lung tissue mechanical changes are a hallmark in bleomycin-induced lung fibrosis [1]. However, inflammatory changes can play also a role, specially in early stages after injury. To ascertain the relative influence of fibrosis and inflammation we have studied a total number of 40 male Sprague-Dawley rats endotracheally instilled with bleomycin (0.25 U/100g body weight) or saline. Animals were sacrificed at 3, 7 or 15 days after instillation. Lung samples were processed for hystochemistry (elastic and collagen fibers), morphometry (air/tissue, cells count), and lung tissue biochemistry [hydroxyprolin (hP), myeloperoxidase (MPO) concentrations]. Lung tissue strips samples were submitted to oscillations with a composite wave of five equal amplitude discrete frequencies ranging between 0.2 and 3.1 Hz. Animals were divided into four groups (control, bleomycin 3rd, 7th and 15th day). One Way Anova showed sig- nificant changes of lung tissue resistance and hysteresivity at low frequencies. Changes in tissue density of elastic, collagen fibers, and the concentration of HP were also significant. Both tissue elastance (all frequencies) and re- sistance (low frequencies) were correlated to MPO concentration (Pearson R: 0.48-0.53, p < 0.005), while hystersivity at low frequencies was correlated to the density of elastic fibers and lung weight. No correlations were observed between collagen density or HP and mechanical tissue changes.

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Page 1: Optimality of the length-to-diameter ratio in the human bronchial tree

$598 Journal o f Biomechanics 2006, Vol. 39 (Suppl 1)

7735 We-Th, no. 23 (P64) Opt imal i ty o f the length-to-diameter ratio in the human bronchial tree E. Lee 1 , M.'~ Kang 2, H.-J. Yang 2, J.W. Lee 2. 1City health Center, Pohang, Korea, 2Department of Mechanical Engineering and also Systems Bio-Dynamics Research Center, Pohang University of Science and Technology, Pohang, Korea

Human bronchial tree has a very complex structure, and the geometric param- eters such as diameter, length and branching angle differ from generation to generation. Of various geometric parameters defining the bronchial structure, the diameter ratio and branching angle at branching has been found to result from an optimality rule, minimizing the pressure loss under a volume constraint condition. This paper extends the optimality rule to show that the nearly constant length-to-diameter ratio observed with conducting airways of human bronchial tree is the result of fluid dynamic optimality. In any branched tube there are two pressure loss mechanisms, one for wall friction in the tube section and the other for flow division in the branching section, and there exists an optimal length-to-diameter ratio which minimizes the total pressure loss for a branched tube in laminar flow condition. The optimal length-to-diameter ratio predicted by the pressure loss minimization shows an excellent agreement with the length-to-diameter ratios found in the human conducting airways.

7779 We-Th, no. 24 (P64) Intravital endo-microscopy of alveoli: a new method to visualize alveolar dynamics C.A. Stahl 1 , S. Schumann 1 , H. Knorpp 1 , M. Schneider 1 , K. MSIler 2, J. Guttmann 1 . 1Department of Anesthesiology and Critical Care Medicine, University of Freiburg, Germany, 2Biomedical Engineering, Furtwangen University, Germany

Introduction: In the frame of protective lung ventilation the alveolar biome- chanics come more and more in the focus of the scientific interest. New microscopic techniques and experimental setups enable a view on the alveoli dynamically changing their geometry under mechanical ventilation [Schiller et al. (2003) CCM 31(4)]. Although of fascinating image quality the alveoli are observed at an open chest wall under a glass plate representing an artificial situation. To circumvent this restriction we developed a method of intravital endo-microscopy and tested it on an animal model (rat). Methods: In cooperation with Schoelly GmbH (Denzlingen, Germany) we developed a rigid endo-microscope. The endoscope tube can be introduced vertically into the thorax by minimally invasive thoracostomy. The system is being placed in the plane of the pleura thus enabling microscopy of in- vivo alveolar dynamics without mechanical deformation of the alveoli under observation. The space between the lens and the lung tissue is flushed with clear fluid. Excess fluid is evacuated through an outer trocar. By applying a few cmH20 of negative pressure to the outer trocar, the lung surface is kept in contact with the inner chest wall. Results: The new optical system provides excellent image quality of subpleural alveoli in the closed chest. The construction of the system and simultaneously acquired video-sequences of microscopic data and PV analyses will be pre- sented. Conclusion: This new minimal invasive method of intravital endo-microscopy enables the observation of the dynamic behaviour of alveoli in the closed chest in situ. The concurrent observation of respiratory mechanics and alveolar dynamics provides a promising tool to correlate global analysis of respiratory mechanics with local alveolar properties.

7022 We-Th, no. 25 (P64) Airway reopening: oscillating air finger propagation through a l iquid-f i l led tube B.J. Smith, D.P. Gaver II1. Tulane University, New Orleans, USA

Acute respiratory distress syndrome (ARDS) is characterized by pulmonary airway collapse and fluid occlusion. Subsequent airway reopening, driven by mechanical ventilation, generates damaging stresses and stress gradients on the airway walls. Through our ongoing research we strive for a thorough understanding of the mechanics of this process, yielding ventilation strate- gies that reduce or eliminate airway epithelial trauma. In the present study we computationally investigate the unsteady propagation of a finger of air through a liquid-filled rigid tube. The system, a free surface with fluid-structure interaction, is modeled using the boundary element method (BEM) coupled to lubrication theory in the upstream thin film region. An axisymmetric model is posed, which consists of a BEM region spanning from the downstream end to a point on the air-liquid interface where small slope assumptions hold. Further upstream, lubrication theory is used to resolve the thin film. The system is governed by three dimensionless parameters: the capillary number Ca = ~tU/y, consisting of mean (Ca M) and sinusoidal oscillatory (Ca~2) compo- nents, represents the balance between viscosity (~t), velocity (U), and surface tension (y). The dimensionless frequency ~2 = ~t(,)R/y and amplitude A = 2Ca~/~2

Poster Presentations

parameterize bubble oscillation. Converging and diverging stagnation points are important for determining the location of surfactant accumulation and deposition, respectively. We find that these stagnation points move dynamically throughout the cycle; typically occurring on the interface at low ~2, these points separate into the bulk of the fluid as ~2 increases. Cycle averaged results show that for increasing ~2 bubble tip velocity increases while residual film thickness decreases accordingly. Cycle-spatial averaging demonstrates an increasing influence of viscous forces on the pressure drop at the bubble tip as ~2 increases, particularly for high amplitude cases. Supported by NASA grant NAG3-2734 and NIH P20-EB001432

4700 We-Th, no. 26 (P64) Direct maximum expiratory f low model ing f rom lung function testing of pediatr ic patients

J. Sznitman 1, B. Spycher 2, U. Frey 3, J.H. Wildhaber 4. 1Institute efFluid Dynamics, ETH Zurich, Switzerland, 2Department of Social and Preventive Medicine, University of Berne, Switzerland, 3pediatric Respiratory Medicine, Department of Pediatrics, University Hospital of Berne, Switzerland, 4Division of Respiratory Medicine, University Children's Hospital Zurich, Switzerland

Since their introduction [1], maximal expiratory flow-volume (MEFV) curves have become a widely used non-invasive lung function test, potentially sensi- tive to respiratory mechanics and obstruction. In asthma, spirometry is consid- ered the standard tool for objective assessment, and lung function parameters, in particular FEV1 (forced exhaled volume in 1 s), are used not only in the assessment of disease severity but also as the primary outcome in clinical studies [2]. However, most asthmatic children have lung function values in the normal range independent of disease severity [3]. Such parameters generally reflect single data points extracted from flow-volume (FV) curves, making their efficacy and interpretation somewhat limited. In the present investigation, we show that rather than using classic lung function parameters, the behavior of FV curves may be better understood based on mathematical differentiation schemes and in particular the definition of convexity. Similar to the concept of slope ratio (SR) based on instantaneous tangent slopes of the FV curve [4], the behavior of the second derivative of the FV curve leads to suitable models describing the configuration of pediatric patient FV curves. In a further step, we show that the definition of a local and average curvature of FV curves may be directly related to expiratory volume acceleration and furthermore used as an index to characterize flow obstruction in asthmatic patients. In the near future, such models may be directly incorporated into spirometric hardware and used in lung function diagnostic.

References [1] Hyatt R.E., et al. J. Appl. Physiol. 1958; 13: 331-336. [2] Bacharier L.B., et al. J. Allergy Clin. Immunol. 2002; 109: 266. [3] Verini M., et al. Allergy Asthma Proc. 2001; 22: 297-302. [4] Mead J. J. Appl. Physiol. 1978; 44: 156-165.

7354 We-Th, no. 27 (P64) Lung tissue mechanics after bleomycin- induced lung injury: Inflammation vs f ibros is M. Pinart 4, A. Serrano 2, E.M. Negri 3, R. Cabrera 1 , P.R.M. Rocco 4, P.V. Romero 1 . 1Laboratory of Experimental Pneumology, IDIBELL, L'Hospitalet, Barcelona, Spain, 2Department of Experimental Pathology, IIBB-CSIC, IDIBAPS, Barcelona, Spain, 3Department of Pathology, Clinical Hospital, University of Sao Paule, Sao Paule, Brazil, 4Laboratory of Respiration Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Lung tissue mechanical changes are a hallmark in bleomycin-induced lung fibrosis [1]. However, inflammatory changes can play also a role, specially in early stages after injury. To ascertain the relative influence of fibrosis and inflammation we have studied a total number of 40 male Sprague-Dawley rats endotracheally instilled with bleomycin (0.25 U/100g body weight) or saline. Animals were sacrificed at 3, 7 or 15 days after instillation. Lung samples were processed for hystochemistry (elastic and collagen fibers), morphometry (air/tissue, cells count), and lung tissue biochemistry [hydroxyprolin (hP), myeloperoxidase (MPO) concentrations]. Lung tissue strips samples were submitted to oscillations with a composite wave of five equal amplitude discrete frequencies ranging between 0.2 and 3.1 Hz. Animals were divided into four groups (control, bleomycin 3rd, 7th and 15th day). One Way Anova showed sig- nificant changes of lung tissue resistance and hysteresivity at low frequencies. Changes in tissue density of elastic, collagen fibers, and the concentration of HP were also significant. Both tissue elastance (all frequencies) and re- sistance (low frequencies) were correlated to MPO concentration (Pearson R: 0.48-0.53, p < 0.005), while hystersivity at low frequencies was correlated to the density of elastic fibers and lung weight. No correlations were observed between collagen density or HP and mechanical tissue changes.