Application of Magnetic Resonance (MR) Imaging for the Development and Validation of Computational Fluid Dynamic (CFD) Models of the Rat Respiratory System

Computational fluid dynamic (CFD) models of the respiratory system provide a quantitative basis for extrapolating the localized dose of inhaled materials and improving human health risk assessments based upon inhalation studies conducted in animals. Nevertheless, model development and validation have historically been tedious and time-consuming tasks. In recognition of this, we previously reported on the use of proton (1H) magnetic resonance (MR) imaging for visualizing nasal-sinus passages in the rat, and for speeding computational mesh generation. Here, the generation and refinement of meshes for rat nasal airways are described in more detail and simulated airflows are presented. To extend the CFD models to the complete respiratory tract, three-dimensional (3D) 1H MR imaging of rat pulmonary casts was also utilized to construct pulmonary airway meshes using procedures developed for the nasal airways. Furthermore, the feasibility of validating CFD predictions with MR was tested by imaging hyperpolarized 3He gas at physiological flow rates in a straight pipe with a diameter comparable to the rat trachea. Results from these diverse studies highlight the potential utility of MR imaging not only for speeding CFD development but also possibly for model validation.

[1]  Scott A. Mitchell,et al.  Quality Mesh Generation in Higher Dimensions , 2000, SIAM J. Comput..

[2]  Kevin R Minard,et al.  T2-shortening of 3He gas by magnetic microspheres. , 2005, Journal of magnetic resonance.

[3]  Imre Balásházy,et al.  Simulation of particle trajectories in bifurcating tubes , 1994 .

[4]  M E Easterly,et al.  A review of high-resolution X-ray computed tomography and other imaging modalities for small animal research. , 2001, Lab animal.

[5]  Julia S Kimbell,et al.  Use of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry comparisons of ester vapors. , 2002, Toxicology and applied pharmacology.

[6]  L W Hedlund,et al.  Sensitivity and resolution in 3D NMR microscopy of the lung with hyperpolarized noble gases , 1999, Magnetic resonance in medicine.

[7]  F H Green,et al.  BRONCHIAL CASTS OF HUMAN LUNGS USING NEGATIVE PRESSURE INJECTION , 2000, Experimental lung research.

[8]  Julia S Kimbell,et al.  Human respiratory tract cancer risks of inhaled formaldehyde: dose-response predictions derived from biologically-motivated computational modeling of a combined rodent and human dataset. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  James M. Pope,et al.  Quantitative NMR imaging of flow , 1993 .

[10]  B. Balcom,et al.  Magnetic Resonance Imaging of Gases: A Single-Point Ramped Imaging withT1Enhancement (SPRITE) Study☆ , 1999 .

[11]  Imre Balásházy,et al.  Deposition of aerosols in asymmetric airway bifurcations , 1995 .

[12]  Prado,et al.  Magnetic Resonance Imaging of Gases: A Single-Point Ramped Imaging with T1 Enhancement (SPRITE) Study. , 1999, Journal of magnetic resonance.

[13]  Benedict Newling,et al.  Velocity imaging of highly turbulent gas flow. , 2004, Physical review letters.

[14]  Richard E. Jacob,et al.  3He spin exchange cells for magnetic resonance imaging , 2002 .

[15]  Melvin E Andersen,et al.  Toxicokinetic modeling and its applications in chemical risk assessment. , 2003, Toxicology letters.

[16]  G Cumming,et al.  Angles of branching and diameters of branches in the human bronchial tree. , 1967, The Bulletin of mathematical biophysics.

[17]  C. Carrington,et al.  Morphometry of the Human Lung , 1965, The Yale Journal of Biology and Medicine.

[18]  H. Schulz,et al.  Reconstruction of the Lung Geometry for the Simulation of Aerosol Transport , 1996 .

[19]  K T Morgan,et al.  Computer simulation of inspiratory airflow in all regions of the F344 rat nasal passages. , 1997, Toxicology and applied pharmacology.

[20]  L W Hedlund,et al.  Detection of emphysema in rat lungs by using magnetic resonance measurements of 3He diffusion. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[21]  L. Hedlund,et al.  MR microscopy of lung airways with hyperpolarized 3He , 1998, Magnetic resonance in medicine.

[22]  R P Subramaniam,et al.  Use of computational fluid dynamics models for dosimetry of inhaled gases in the nasal passages. , 2001, Inhalation toxicology.

[23]  A. Kuprat Adaptive smoothing techniques for 3-D unstructured meshes , 1996 .

[24]  D. McRobbie,et al.  Studies of the human oropharyngeal airspaces using magnetic resonance imaging. I. Validation of a three-dimensional MRI method for producing ex vivo virtual and physical casts of the oropharyngeal airways during inspiration. , 2003, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[25]  L W Hedlund,et al.  Registered 1H and 3He magnetic resonance microscopy of the lung , 2001, Magnetic resonance in medicine.

[26]  Ashutosh Chaturvedi,et al.  Three-dimensional segmentation and skeletonization to build an airway tree data structure for small animals , 2005, Physics in medicine and biology.

[27]  Imre Balásházy,et al.  Particle deposition in airway bifurcations–II. Expiratory flow , 1993 .

[28]  Geoffrey McLennan,et al.  CT-based geometry analysis and finite element models of the human and ovine bronchial tree. , 2004, Journal of applied physiology.

[29]  Paul T. Callaghan,et al.  Pulsed-Gradient Spin-Echo NMR for Planar, Cylindrical, and Spherical Pores under Conditions of Wall Relaxation , 1995 .

[30]  Andrew P. Kuprat,et al.  Volume conserving smoothing for piecewise linear curves, surfaces, and triple lines , 2001 .

[31]  V. Callot,et al.  Helium-3 MRI diffusion coefficient: correlation to morphometry in a model of mild emphysema , 2003, European Respiratory Journal.

[32]  J.E.A. Reinders,et al.  Flow measurements with NMR. , 1986 .

[33]  Janez Stepišnik,et al.  Measuring and imaging of flow by NMR , 1985 .

[34]  Jeffry D Schroeter,et al.  Risk assessment dosimetry model for inhaled particulate matter: II. Laboratory surrogates (rat). , 2003, Toxicology letters.

[35]  Ananth V. Annapragada,et al.  Computational Fluid Dynamics Simulation of Airflow and Aerosol Deposition in Human Lungs , 2004, Annals of Biomedical Engineering.

[36]  I. Katz,et al.  Deposition Patterns of Polydisperse Aerosols Within Human Lungs , 1993 .

[37]  K T Morgan,et al.  Application of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat. , 1993, Toxicology and applied pharmacology.

[38]  C Kleinstreuer,et al.  Effects of curved inlet tubes on air flow and particle deposition in bifurcating lung models. , 2001, Journal of biomechanics.

[39]  Bastiaan Driehuys,et al.  Hybrid spin-exchange optical pumping of 3He. , 2003, Physical review letters.

[40]  Joy Conway,et al.  Simulation of the regional manifestation of asthma. , 2004, Journal of pharmaceutical sciences.

[41]  Janez Stepis Nik,et al.  Validity limits of Gaussian approximation in cumulant expansion for diffusion attenuation of spin echo , 1999 .

[42]  James A. Sethian,et al.  Level Set Methods and Fast Marching Methods , 1999 .

[43]  Bien Chann,et al.  Production of highly polarized 3He using spectrally narrowed diode laser array bars , 2003 .

[44]  D. Cory,et al.  Sensitivity and Resolution of Constant-Time Imaging , 1994 .

[45]  C Timchalk,et al.  Potential technology for studying dosimetry and response to airborne chemical and biological pollutants , 2001, Toxicology and industrial health.

[46]  Dongming Hwang,et al.  In silico modeling of asthma. , 2003, Advanced drug delivery reviews.

[47]  P. J. Hunter,et al.  Generation of an Anatomically Based Three-Dimensional Model of the Conducting Airways , 2000, Annals of Biomedical Engineering.

[48]  T. Walker,et al.  Spin-exchange optical pumping of noble-gas nuclei , 1997 .

[49]  Julia S. Kimbell,et al.  Method for obtaining accurate geometrical coordinates of nasal airways for computer dosimetry modeling and lesion mapping , 1995 .

[50]  Julia S. Kimbell,et al.  COMPUTATIONAL FLUID DYNAMICS SIMULATIONS OF INSPIRATORY AIRFLOW IN THE HUMAN NOSE AND NASOPHARYNX , 1998 .

[51]  Paul-Louis George,et al.  Quality mesh generation , 2000 .

[52]  Thomas Meersmann,et al.  Dynamic NMR Microscopy of Gas Phase Poiseuille Flow , 2001 .

[53]  C Kleinstreuer,et al.  Targeted drug aerosol deposition analysis for a four-generation lung airway model with hemispherical tumors. , 2003, Journal of biomechanical engineering.

[54]  D. G. Cory,et al.  Constant time imaging approaches to NMR microscopy , 1997, Int. J. Imaging Syst. Technol..

[55]  Ted B Martonen,et al.  Issues in drug delivery: concepts and practice. , 2005, Respiratory care.