1
Track 14. Cardiovascular Mechanics 14.1. Aneurysms $603 regional tissue pressures and a pseudo-elastic strain energy function defines the stress-strain behavior of the lung tissue. These pressures are used in the relationship between pressure and airway radius and as regional alveolar pressures that act as boundary conditions for the flow solution. Initial studies compared the flow component of the model with symmetrical, Horsfield and anatomical (physically realistic) airway geometries to investigate the influence that branching geometry and dimensional asymmetry has on the air flow distribution. The coupled model is used to compare flow distribution and flow-volume loops in a normal human lung undergoing quiet breathing while exposed to different gravities and in different orientations. Results from the isolated flow model and the fully coupled system demonstrate consistency with earlier symmetrical models and with physiological measurements. However, the accuracy of the predictions is sensitive to the accuracy of the strain energy function used for the lung tissue elasticity. 4158 We-Th, no. 47 (P65) Understanding lung function and remodeling by a novel experimental model of severe allergic inflammation P.R.M. Rocco 1, EL. Silva 1, C.P. Passaro1, V.R. Cagido2, M. Bozza3, M. Dolhnikoff 4, E.M. Negri4, V.L. Capelozzi 4, W.A. Zin 2. 1Laboratory of Pulmonary Investigation, 2Laboratory of Respiration Physiology, Carlos Chagas Filho Biophysics Institute, 3Institute of Microbiology, Federal University of Rio de Janeiro, Brazil, 4Department of Pathology, University of S#o Paulo, S#o Paulo, Brazil The aim of the study is to develop a murine model of severe allergic lung inflam- mation that could mimic the lung morphofunctional and immunological changes characteristic of human severe asthma as closely as possible. In vivo (resistive and viscoelastic pressures, and static elastance) and in vitro (tissue elastance, resistance, and hysteresivity) respiratory mechanics, lung histology (light and electron microscopy), quantitative analysis of collagen and elastic fiber in airway and lung parenchyma, and cellular profile, IL-4, IL-5, and IL-13 levels in the bronchoalveolar lavage fluid were evaluated. Eighteen BALB/c mice were randomly divided into three groups. In the severe (SA) and fatal (FA) allergic lung inflammation groups, mice were sensitized with ovalbumin and exposed to repeated intratracheal ovalbumin challenges; but in FA group methacholine was intravenously injected at the moment of the experiment. The control group received saline using the same protocol. Resistive and viscoelastic pressures, static elastance, tissue resistance and elastance increased progressively from control to SA and FA groups. Both SA and FA groups showed a marked cellular infiltration with eosinophils and neutrophils in lung tissue and airways, mucus metaplasia, hypertrophy/hyperplasia of the airway smooth muscles, thickening of the basement membrane, fibrosis in airway and lung parenchyma, and an increase in IL-4, IL-5, and IL-13 levels. In conclusion, these models of SA and FA showed functional, histological, and immunological changes, similar to those observed in human severe asthma. Thus, they provide opportunities to explore basic issues of susceptibility, mechanism, and risk, albeit with the limitations of extrapolation. Supported by: CNPq, FAPERJ, PRONEX-FAPERJ 7933 We-Th, no. 48 (P65) In situ imaging of collagen gel with a second-harmonic generation microscope R. Nakayama, S. Fukushima, T. Yasui, T. Araki. Graduate School of Engineering Science, Osaka University, Osaka, Japan Collagen is a main component of extracellar matrix and relates to deformability of respiratory tissue. Because the mechanical stimuli due to the deformation af- fect to the function of pulmonary cells, in situ observation of dynamical change of collagen structure is essential for the clarification of the cellular function. However, the dynamical change cannot be observed by conventional methods, such as histochemical staining, electron microscopy, X-ray diffraction method. Instead of these invasive methods, we proposed a noninvasive method with second-harmonic generation (SHG) light. Collagen molecules emit SHG light because of its non centrosymmetrical triple helix structure. Therefore, SHG microscopy provides selective detection of collagen structure. In this study, we quantitatively evaluated the dependence of collagen concentration and fiber orientation on the intensity of SHG light with various type I collagen gels, and performed three-dimensional SHG imaging of cell embedded collagen gel. For the evaluation of the orientation dependence, we prepared an ordered collagen gel, where strain of 30% was loaded by uniaxial compression. The SHG microscope used for this study consists of a mode-locked Ti:Sapphire laser (wavelength 800 nm) and an inverted microscope. The laser pulse was focused onto the sample with an objective, and the SHG light emitted from the sample was detected by a photomultiplier tube. The mean intensity of the SHG light from the collagen gels of which concentration varied from 1.0 to 3.0 mg/ml was proportionally increased with the concentration. Although the collagen concentration of the ordered gel was same as that of a control gel, the mean intensity of SHG light from the ordered gel increased 65% by comparing the control. These results shows SHG light intensity was sensitive not only to collagen concentration but to fiber orientation. Furthermore SHG images clearly captured fibrous patterns and reconstruction of collagen gel. Therefore, SHG microscopy is useful for detection of the dynamical interaction between cells and extracellular matrix. Track 14 Cardiovascular Mechanics 14.1. Aneurysms 4859 Mo-Tu, no. 1 (P65) Computational haemodynamics in cerebral aneurysm custom models based on different reconstructive methodologies L. Socci, G. Pennati, E Migliavacca, G. Dubini. Laboratory of Biological Structure Mechanics, Structural Engineering Department, Politecnico di Milano, Milan, Italy Introduction: Haemodynamic factors are thought to be implicated in the progression and rupture of saccular intracranial aneurysms occurring at bi- furcations of the circle of Willis and its proximal branches. The coupling of computational fluid dynamics analyses with high-resolution imaging techniques is a valid method to evaluate the local haemodynamics in complex anatomies. Realistic patient-specific models are necessary to give insights into the cerebral haemodynamics due to large variability among individual anatomies. Numer- ous investigations aimed to associate haemodynamic characteristics, such as wall shear stresses and extent of intra-aneurismal flow patterns, with origin and development of aneurysms. These quantities are expected to be critically dependent on the vascular geometric details, such as vessel tortuosity or wall roughness. The objective of this work is to evaluate the sensitivity of the cerebral aneurysms haemodynamics to the computational model geometry of specific patients; the adopted geometries are obtained according to different reconstruction techniques based on magnetic resonance images. Methods: Three different reconstruction techniques were used. The first two procedures were based on a commercial code (Amira, Mercury Computer Systems Inc.): the first technique uses an automatic segmentation algorithm, whereas in the second one a smoothing procedure was applied. In the last technique, circular tubes with regularly variable diameters following the vessel paths were used to built the models. Haemodynamic simulations were performed by using a commercial code (Fluent, Fluent Inc.) and the sensitivity analysis of the haemodynamic features to the above geometrical models were done. Results and Conclusions: Comparison of geometrical reconstructed mod- els showed substantial differences in terms of vessel distortion and surface irregularities; consequently, the haemodynamics features differ as well. Proper smoothing is necessary to obtain feasible computational models. Nevertheless, since we do not know the actual geometries, it is not possible to assess the discrepancies of computed results versus the in vivo cerebral aneurysms haemodynamics. 5854 Mo-Tu, no. 2 (P65) Mechanical properties of intraluminal thrombus from abdominal aortic aneurysm under compressive loads E Boschetti 1, M. Camera2,3, L. Socci 1, R. Spirito4, E.S. Di Martino5. 1Laboratory of Biological Structure Mechanics, Dipartimento di Ingegneria Strutturale, Politecnico di Milano, Milano, Italy, 2Dipartimento di Scienze Farmacologiche, Universita degli Studi di Milano, Milano, Italy, 3Laboratory of Ceil Biology and Biochemistry of Atherothrombosis, Centro Cardiologico Monzino, Milano, Italy, 4Vascular Surgery Unit, Centro Cardiologico Monzino, Milano, Italy, 5Institute for Complex Engineered Systems and Biomedical Engineering Department, Carnegie Mellon University, Pittsburgh, USA Computational models, developed to study abdominal aortic aneurysm (AAA) biomechanics, demonstrated that the presence of an intraluminal thrombus (ILT) can significantly alter the wall stress distribution in the degenerated vessel wall. ILT is a soft hydrated tissue constituted of 90% of water that can be described by the biphasic theory developed by Mow. Although the ILT is subjected to compression in vivo, up to now ILT constitutive models have been based on parameters derived from tensile testing of ILT specimens. The aim of this study was to define the biomechanical properties of ILT under compressive loads, using a biphasic approach. To this aim, ILTs were removed from patients undergoing surgical AAA resection. From each ILT we obtained several samples representing different transmural layers. The ILT samples were then tested for confined and unconfined compression and underwent

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Page 1: Understanding lung function and remodeling by a novel experimental model of severe allergic inflammation

Track 14. Cardiovascular Mechanics 14.1. Aneurysms $603

regional tissue pressures and a pseudo-elastic strain energy function defines the stress-strain behavior of the lung tissue. These pressures are used in the relationship between pressure and airway radius and as regional alveolar pressures that act as boundary conditions for the flow solution. Initial studies compared the flow component of the model with symmetrical, Horsfield and anatomical (physically realistic) airway geometries to investigate the influence that branching geometry and dimensional asymmetry has on the air flow distribution. The coupled model is used to compare flow distribution and flow-volume loops in a normal human lung undergoing quiet breathing while exposed to different gravities and in different orientations. Results from the isolated flow model and the fully coupled system demonstrate consistency with earlier symmetrical models and with physiological measurements. However, the accuracy of the predictions is sensitive to the accuracy of the strain energy function used for the lung tissue elasticity.

4158 We-Th, no. 47 (P65) Understanding lung function and remodeling by a novel experimental model of severe allergic inflammation

P.R.M. Rocco 1 , EL. Silva 1, C.P. Passaro 1, V.R. Cagido 2, M. Bozza 3, M. Dolhnikoff 4, E.M. Negri 4, V.L. Capelozzi 4, W.A. Zin 2. 1Laboratory of Pulmonary Investigation, 2Laboratory of Respiration Physiology, Carlos Chagas Filho Biophysics Institute, 3Institute of Microbiology, Federal University of Rio de Janeiro, Brazil, 4Department of Pathology, University of S#o Paulo, S#o Paulo, Brazil

The aim of the study is to develop a murine model of severe allergic lung inflam- mation that could mimic the lung morphofunctional and immunological changes characteristic of human severe asthma as closely as possible. In vivo (resistive and viscoelastic pressures, and static elastance) and in vitro (tissue elastance, resistance, and hysteresivity) respiratory mechanics, lung histology (light and electron microscopy), quantitative analysis of collagen and elastic fiber in airway and lung parenchyma, and cellular profile, IL-4, IL-5, and IL-13 levels in the bronchoalveolar lavage fluid were evaluated. Eighteen BALB/c mice were randomly divided into three groups. In the severe (SA) and fatal (FA) allergic lung inflammation groups, mice were sensitized with ovalbumin and exposed to repeated intratracheal ovalbumin challenges; but in FA group methacholine was intravenously injected at the moment of the experiment. The control group received saline using the same protocol. Resistive and viscoelastic pressures, static elastance, tissue resistance and elastance increased progressively from control to SA and FA groups. Both SA and FA groups showed a marked cellular infiltration with eosinophils and neutrophils in lung tissue and airways, mucus metaplasia, hypertrophy/hyperplasia of the airway smooth muscles, thickening of the basement membrane, fibrosis in airway and lung parenchyma, and an increase in IL-4, IL-5, and IL-13 levels. In conclusion, these models of SA and FA showed functional, histological, and immunological changes, similar to those observed in human severe asthma. Thus, they provide opportunities to explore basic issues of susceptibility, mechanism, and risk, albeit with the limitations of extrapolation. Supported by: CNPq, FAPERJ, PRONEX-FAPERJ

7933 We-Th, no. 48 (P65) In situ imaging of collagen gel with a second-harmonic generation microscope R. Nakayama, S. Fukushima, T. Yasui, T. Araki. Graduate School of Engineering Science, Osaka University, Osaka, Japan

Collagen is a main component of extracellar matrix and relates to deformability of respiratory tissue. Because the mechanical stimuli due to the deformation af- fect to the function of pulmonary cells, in situ observation of dynamical change of collagen structure is essential for the clarification of the cellular function. However, the dynamical change cannot be observed by conventional methods, such as histochemical staining, electron microscopy, X-ray diffraction method. Instead of these invasive methods, we proposed a noninvasive method with second-harmonic generation (SHG) light. Collagen molecules emit SHG light because of its non centrosymmetrical triple helix structure. Therefore, SHG microscopy provides selective detection of collagen structure. In this study, we quantitatively evaluated the dependence of collagen concentration and fiber orientation on the intensity of SHG light with various type I collagen gels, and performed three-dimensional SHG imaging of cell embedded collagen gel. For the evaluation of the orientation dependence, we prepared an ordered collagen gel, where strain of 30% was loaded by uniaxial compression. The SHG microscope used for this study consists of a mode-locked Ti:Sapphire laser (wavelength 800 nm) and an inverted microscope. The laser pulse was focused onto the sample with an objective, and the SHG light emitted from the sample was detected by a photomultiplier tube. The mean intensity of the SHG light from the collagen gels of which concentration varied from 1.0 to 3.0 mg/ml was proportionally increased with the concentration. Although the collagen concentration of the ordered gel was same as that of a control gel, the

mean intensity of SHG light from the ordered gel increased 65% by comparing the control. These results shows SHG light intensity was sensitive not only to collagen concentration but to fiber orientation. Furthermore SHG images clearly captured fibrous patterns and reconstruction of collagen gel. Therefore, SHG microscopy is useful for detection of the dynamical interaction between cells and extracellular matrix.

Track 14

Cardiovascular Mechanics

14.1. Aneurysms 4859 Mo-Tu, no. 1 (P65) Computational haemodynamics in cerebral aneurysm custom models based on different reconstructive methodologies L. Socci, G. Pennati, E Migliavacca, G. Dubini. Laboratory of Biological Structure Mechanics, Structural Engineering Department, Politecnico di Milano, Milan, Italy

Introduction: Haemodynamic factors are thought to be implicated in the progression and rupture of saccular intracranial aneurysms occurring at bi- furcations of the circle of Willis and its proximal branches. The coupling of computational fluid dynamics analyses with high-resolution imaging techniques is a valid method to evaluate the local haemodynamics in complex anatomies. Realistic patient-specific models are necessary to give insights into the cerebral haemodynamics due to large variability among individual anatomies. Numer- ous investigations aimed to associate haemodynamic characteristics, such as wall shear stresses and extent of intra-aneurismal flow patterns, with origin and development of aneurysms. These quantities are expected to be critically dependent on the vascular geometric details, such as vessel tortuosity or wall roughness. The objective of this work is to evaluate the sensitivity of the cerebral aneurysms haemodynamics to the computational model geometry of specific patients; the adopted geometries are obtained according to different reconstruction techniques based on magnetic resonance images. Methods: Three different reconstruction techniques were used. The first two procedures were based on a commercial code (Amira, Mercury Computer Systems Inc.): the first technique uses an automatic segmentation algorithm, whereas in the second one a smoothing procedure was applied. In the last technique, circular tubes with regularly variable diameters following the vessel paths were used to built the models. Haemodynamic simulations were performed by using a commercial code (Fluent, Fluent Inc.) and the sensitivity analysis of the haemodynamic features to the above geometrical models were done. Results and Conclusions: Comparison of geometrical reconstructed mod- els showed substantial differences in terms of vessel distortion and surface irregularities; consequently, the haemodynamics features differ as well. Proper smoothing is necessary to obtain feasible computational models. Nevertheless, since we do not know the actual geometries, it is not possible to assess the discrepancies of computed results versus the in vivo cerebral aneurysms haemodynamics.

5854 Mo-Tu, no. 2 (P65) Mechanical properties of intraluminal thrombus from abdominal aortic aneurysm under compressive loads

E Boschetti 1 , M. Camera 2,3, L. Socci 1 , R. Spirito 4, E.S. Di Martino 5. 1Laboratory of Biological Structure Mechanics, Dipartimento di Ingegneria Strutturale, Politecnico di Milano, Milano, Italy, 2 Dipartimento di Scienze Farmacologiche, Universita degli Studi di Milano, Milano, Italy, 3Laboratory of Ceil Biology and Biochemistry of Atherothrombosis, Centro Cardiologico Monzino, Milano, Italy, 4Vascular Surgery Unit, Centro Cardiologico Monzino, Milano, Italy, 5Institute for Complex Engineered Systems and Biomedical Engineering Department, Carnegie Mellon University, Pittsburgh, USA

Computational models, developed to study abdominal aortic aneurysm (AAA) biomechanics, demonstrated that the presence of an intraluminal thrombus (ILT) can significantly alter the wall stress distribution in the degenerated vessel wall. ILT is a soft hydrated tissue constituted of 90% of water that can be described by the biphasic theory developed by Mow. Although the ILT is subjected to compression in vivo, up to now ILT constitutive models have been based on parameters derived from tensile testing of ILT specimens. The aim of this study was to define the biomechanical properties of ILT under compressive loads, using a biphasic approach. To this aim, ILTs were removed from patients undergoing surgical AAA resection. From each ILT we obtained several samples representing different transmural layers. The ILT samples were then tested for confined and unconfined compression and underwent