Working Group 3: Macro-To-Micro Scale Imaging and Transport in Biological Systems

Working Group Lead: Yoonsuck Choe (

Goals and Objectives: The goal of Working Group 3 is to share techniques, experience, models, and modeling philosophy in the simulation of transport processes in human systems that span the macro [O(10^-3-10^-1 m)] through micro [O(10^-5-10^-3 m)] scales. Broadly, this technology includes incorporation of physiological geometry through medical imaging techniques, the discretization and solution of field transport equations relevant to the system at hand, and the approaches used to communicate geometric and transport parameters between macro and micro scales.

The human systems represented by current particpants include digestive, circulatory and respiratory. Imaging/geometry specification issues common to simulating these systems include: segmentation, thinning, space-time resolution, microscale geometric representation/coupling, and automation. Transport modeling issues common to simulating these systems include: specification of appropriate field equations, boundary condition specification, fluid-structure interactions, turbulence/transition, space-time resolution, microscale physics representation/coupling, deposition modeling, diffusion modeling, numerical discretization accuracy, high performance computing and automation.

Working Group 3 Participants

This working group is also linked with Working Group 7 Multiscale Imaging.

Approach: During our first year, the WG3 particpants explored a number of model sharing strategies and settled on the following:

1) Web interactions via a web conferencing tool (we use Breeze) is an effective way to get us all together and exchange information on a number of levels including both technical and administrative, both formal and casual, both with and without video, both verbal and written (using desktop sharing of applications, files, whiteboards.)

2) The most useful way for practitioners in macro-through-micro modeling of biological systems to exchange modeling approaches is through technical, nuts and bolts webinars. We have held several of these to date (see Presentations below) and our approach is to continue to schedule, notify potential interested parties, and broadcast these via Breeze in the context of WG3.

Currently, all active and observer members of WG3, including non-IMAG observers, are notified of each webinar by e-mail and through the Wiki.



February 5, 2010; 1pmET IMAG Webinar on OpenFOAM

Presented by Rob Kunz, Penn State University
Title: OpenFOAM as a Model Sharing Environment for Macro-Microscale Biomedical Simulation
OpenFOAM Abstract
Presentation Slides

Tuesday June 23, 2009 4-5pm EDT - Stephen J. Smith, Stanford University

  • Title: Synapse Classification for Circuit Reconstruction: The Synaptome Meets the Connectome
  • Authors: Stephen J Smith, Kristina Micheva, JoAnn Buchanan, Nancy O’Rourke, Brad Busse, Nick Weiler.
  • Affiliation: Dept. of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.

Useful circuit reconstruction requires the identification of circuit components as well as the abstraction of circuit connectivity diagrams. In reconstructing (or “reverse‐engineering”) human‐engineered circuits, the challenges of component identification are usually relatively inconsequential, because component diversity is small, and much is generally known in advance, including appropriate component classification schemes (e.g., mosfet, capacitor, etc.). In the case of neural circuits, however, the identification of component properties involves challenges that may be far more formidable. Both gene expression and physiological data suggest today that neural circuit components, such as synapses and dendrites, could be almost limitless in their molecular, structural and functional diversity.

We are using array tomography (Micheva & Smith, Neuron, 55:25‐36, 2007) to: (1) empirically define the extent of synapse molecular and structural diversity, (2) discover categories that encapsulate the major components of synapse diversity (i.e., a “Synaptome”), and, (3) identify a compact set of markers optimal to classify synapses during high‐throughput connectomic imaging. We have chosen rectangular slabs of mouse somatosensory cortex that extend through the entire cortical depth as a representative and amenable “microcosm” of CNS circuitry. We are using a panel of antibody markers chosen to identify synapse classes that might be based, for instance, on differing neurotransmitter receptor and transporter types. We anticipate that a synaptome will prove useful as a framework for the better understanding of the large‐scale circuit connectivity diagrams that will be connected in the years ahead by means such as KESM, and for better understanding the differential susceptibilities of subsets of neurons and synapses to neurodevelopmental and neurodegenerative disorders.

Supported by grants from the NIH (NS054252; NS063210), the McKnight Endowment Fund for Neuroscience, the Howard Hughes Medical Foundation, and the Gatsby Charitable Foundation.

YouTube videos: search for "TheSmithlab", one example: (choose HQ or HD option for best results)



Wednesday February 25, 2009 - Rob Kunz, D. C. Haworth, A. Kriete, Penn State University

Geometric and Fluid Flow Coupling Between Macro and Micro Scales in Respiration Simulation

Presentation Abstract

Presentation Slides

This talk summarizes the now winding down IMAG project: “Multi-Scale Human Respiratory System Simulations to Study the Health Effects of Aging, Disease and Inhaled Substances”. This research has resulted in an end-to-end medical image through CFD process that can be used to assess pulmonary processes in live patients. It is being communicated to the community through WG3, journal articles, conference presentations, theses and invited lectures.

This talk will focus on all elements of the research including: 1) CT scan processing (segmentation of lobes and upper airway trees), 2) Airway centerline definition  skeleton representation, 3) Generation partitioning, 4) Upper branch truncation, 5) Octree based CFD grid generation, 6) Lobe volume filling, including a new algorithm for doing so in the context of unsteady breathing simulations, 7) Quasi-one-dimensional lower-bronchiole representation using arbitrary polyhedra, 8) Geometric interfacing of macro-to-micro scale representations into a global mesh, 9) Fluid mechanics interfacing of macro-to-micro scale representations, 10) Novel “piston” boundary conditions to naturally accommodate breathing simulations, 11) A fluid-structure interaction framework, 12) Incorporation of oro-pharyngeal geometry, and external atmosphere geometry, 13) The importance of Womersley number and boundary condition order of accuracy on solution accuracy for macro-scale truncated models, 14) Domain decomposition, 15) Single phase and multi-phase CFD simulation on parallel systems, including physical models appropriate for transport of inhaled substances.

Each of these components is semi- or fully-automated, and together, they are embedded within a python-based patient specific framework which can be used for end-to-end medical image through CFD processing of patient-specific pulmonary processes assessments in live patients. The interfaces for each of these components are defined in a fashion that the user can swap out their own modules while retaining the overall functionality of the system. The python framework and the module interfaces will be discussed as well.


Kunz Breeze presentation to group, March 29, 2007

Kunz APS presentation, November 21, 2006

Brasseur Breeze presentation to WG3 on 18 May 2007 entitled "Simulation of Multi-scale Mixing in the Small Intestine Using the Lattice-Boltzmann Method"

Karniadakis Breeze presentation to WG3 on 27 July 2007 entitled "Interface Conditions for Scalable Simulations of the Arterial-Tree on the TeraGrid"

Choe Breeze presentation to WG3 on 24 August 2007 entitled "Data Processing for Serial Sectioning Microscopy of Neural and Vascular Microstructure"

  • Links to movies shown during Choe's presentation
  1. KESM cutting
  2. Raw data and data fly-throughs
  3. 3D reconstruction

Andres Kriete presentation to WG3 on 27 October 2007 entitled "Lung Modeling based on Multiscale Data"

Lin Breeze presentation to WG3 on 9 November 2007 entitled "Large Scale Computing and Visualization for Cardiopulmonary Imaging"

Wilson Breeze presentation to WG3 on 7 December 2007 entitled "Imaging Cells at Nanometer Resolution"

Journal Articles

Choi, J., G. Xia, MH Tawhai, EA Hoffman, and C-L Lin, “Numerical study of high frequency oscillatory air flow and convective mixing in a CT-based human airway model,” DOI: 10.1007/s10439-010-0110-7, Annals of Biomedical Engineering, 2010.

Yin, Y., J. Choi, E.A. Hoffman, M.H. Tawhai, and C.-L. Lin, “Simulation of pulmonary air flow with a subject-specific boundary condition,” doi:10.1016/j.jbiomech.2010.03.048, available online, Journal of Biomechanics, 2010.

Xia, G., M. H. Tawhai, E. A. Hoffman, and C.-L. Lin, “Airway Wall Stiffness and Peak Wall Shear Stress: A Fluid-Structure Interaction Study in Rigid and Compliant Airways,” Annals of Biomedical Engineering, 38(5), 1836-1853, 2010.

Choi, J., M. H. Tawhai, E.A. Hoffman, and C.-L. Lin, “On intra- and intersubject variabilities of airflow in the human lungs,” Physics of Fluids, Vol. 21, 101901, 2009.

Yin, Y., E. A. Hoffman, and C.-L. Lin, “Mass preserving non-rigid registration of CT lung images using cubic B-spline,” Medical Physics, Vol. 36(9), pp. 4213-4222, 2009.

Yin, Y., E. A. Hoffman, and C.-L. Lin, “Local tissue-weight-based nonrigid registration of lung images with application to regional ventilation”, SPIE Medical Imaging, Vol. 7262, p. 72620C, 2009.

Tawhai, M. H., M. P. Nash, C.-L. Lin, and E. A. Hoffman, “The influence of supine and prone posture on regional lung density and pleural pressure gradients in the human lung”, Journal of Applied Physiology, 107: 912-920, 2009.

Kumar, H., M. H. Tawhai, E.A. Hoffman, and C.-L. Lin, “The effects of geometry on airflow in the acinar region of the human lung,” Journal of Biomechanics, Vol. 42(11), pp. 1635-1642, 2009.

Tawhai, M. H., E. A. Hoffman, and C.-L. Lin, “The Lung Physiome: merging imaging-based measures with predictive computational models of structure and function,” Wiley Interdisciplinary Reviews: Systems Biology and Medicine, Vol. 1(1), pp. 61-72, 2009.

Lin, C.-L., M. H. Tawhai, G. McLennan, and E.A. Hoffman, “Multiscale Simulation of Gas Flow in Subject-Specific Models of the Human Lung,” IEEE Engineering in Medicine and Biology, Vol. 28(3), pp. 25-33, 2009.

Xia, G. and C.-L. Lin, ``An Unstructured Finite Volume Approach for Structural Dynamics in Response to Fluid Motions", Computers and Structures, Vol. 86, pp. 684-701, 2008.

Lin, C.-L., M. H. Tawhai, G. McLennan, and E.A. Hoffman, ``Characteristics of the turbulent laryngeal jet and its effect on airflow in the human intra-thoracic airways," Respiratory Physiology & Neurobiology, Vol. 157, pp. 295-309, 2007.

Kabilan, S., C.-L. Lin, and E. A. Hoffman, ``Characteristics of Airflow in a CT-based Ovine Lung: A Numerical Study," Journal of Applied Physiology, Vol. 102, pp. 1469-1482, 2007.

Lin, C.-L. and E.A. Hoffman, “A numerical study of gas transport in human lung models," SPIE Medical Imaging: Physiology, Function, and Structure from Medical Images, Vol. 5746, pp. 92-100, 2005.

Hoffman, E.A., A.V. Clough, G.E. Christensen, C.-L. Lin, G. McLennan, J.M. Reinhardt, B.A. Simon, M. Sonka, M.H. Tawhai, E.J.R. van Beek, G. Wang, ``The Comprehensive Imaging-based Analysis of the Lung: A Forum for Team Science," Academic Radiology, Vol. 11, No. 12, pp. 1370-1380, 2004.

Other Publications

Physiome, Biomedical Computation Review, NIH Center Simbios, Stanford University, 2010

Particle transport in the human lungs, Institute for Clinical and Translational Science, NIH CTSA consortium, University of Iowa, 2010

Virtual Breath, Texas Advanced Computing Center , 2009

Kunz, R.F., Haworth, D.C., Porzio, D.P., Kriete, A., "Progress Towards a Medical Image through CFD Analysis Toolkit for Respiratory Function Assessment on a Clinical Time Scale, Invited Talk and Paper, ISBI 2009, Boston. Paper

Past Events

November 19, 2008

Society for Neuroscience 2008 Minisymposium on High-Throughput Microscopy and Computational/Theoretical Challenges in the Analysis of Neural Circuit Structure. Minisymposium archive (slides, etc.)

Chair: Louise C. Abbott, Co-chair: Yoonsuck Choe


March 29, 2007

Rob Kunz presentation of his IMAG sponsored research in a WG3 Breeze conference

Title: Details of Macro-CFD to Quasi-1D Flow Interfacing in Respiratory System

May 18, 2007

Jim Brasseur presentation of his IMAG sponsored research in a WG3 Breeze conference

Title: Simulation of Multi-scale Mixing in the Small Intestine Using the Lattice-Boltzmann Method

July 27, 2007

George Karniadakis presentation of his IMAG sponsored research in a WG3 Breeze conference

Title: Interface Conditions in Multiscale Modeling of Arterial Trees

August 24, 2007

Yoonsuck Choe presentation of his IMAG sponsored research in a WG3 Breeze conference

Title: Multiscale Imaging and Image Analysis


October 27, 2007

Andres Kriete presentation of his IMAG sponsored research in a WG3 Breeze conference

Title: Lung Modeling Based on Multiscale Data


November 9, 2007

Ching-Long Lin presentation of his IMAG sponsored research in a WG3 Breeze conference

Title: Large-scale Computing and Visualization for Cardiopulmonary Imaging

December 7, 2007

Bridget Wilson presentation of her research in a WG7/WG3 Breeze conference

Title: Imaging Cells at Nanometer Resolution


Monthly Reports

Working Group 3 reports since May 2007 merger with WG7:


Working Group 3 reports prior to May 2007:

March 2006April 2006May 2006June 2006July 2006August 2006September 2006November 2006January 2007February 2007

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