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Adult human tracheobronchial tree

Multiscale Human Respiratory System Simulations to Study Health Effects

Contents

• Contact Information
• Funding Agency 
• Research Emphasis 
• Disease Focus 
• Scales Examined 
• Biomedical, Biological &  Behavioral Areas
• Modeling Methods & Tools  
• Software Development 

Contact Information

Principal Investigator/Contact
Robert Kunz
Pennsylvania State University
Phone: (814) 865-2144
Fax: (814) 865-8896
E-mail: rfk102@only.arl.psu.edu
Project Websites: http://www.personal.psu.edu/faculty/r/f/rfk102/NIH_Multiscale.html

Co-PIs and Collaborators
Daniel Haworth
Pennsylvania State University

Andreas Kriete
Drexel University 

Grant Number - 1-R01-ES-014483-01

Funding Agency

National Institute of Environmental Health Sciences (NIH-NIEHS)

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Research Emphasis

A multi-scale strategy is proposed to develop, couple, apply, and validate multimodality imaging and physics modeling of resolvable and sub-resolvable scales in human respiration. High-resolution computed tomography (HRCT) will be used to characterize the "macroscale" convective range of the lung. Microscopic computed tomography ('CT), and confocal microscopy (CLSM), will be used to characterize the "microscale" global and cellular architectures of the respiratory units. Multiphase computational fluid dynamics and quasi-one-dimensional functional modeling will be used to simulate the multi-component fluid mechanics at the macro- and micro-scales, respectively. Software infrastructure and two-phase fluid mechanics models will be developed to address the coupling between the physics at these two scales. Model predictions will be validated against experimental and clinical data from the literature.

A novel and critical element of the proposed research is that the interfaces between functional biological scales will be developed using dimension-reducing coupling strategies and multidisciplinary data-exchange standards. Coupling technologies will be developed between macro- and microscales, and between imaging and physical modeling; these will yield a system-level model that accommodates the critical two-way coupling between convective respiration physics and uptake, deposition, and disease-state morphology. Such an integrated approach will elucidate heretofore inaccessible physical understanding, dependencies, and treatment implications.

The ultimate public health goal of the research is improved understanding of respiratory function and disease, and evaluation/assessments of the effects of therapies, injury, surgical intervention, and aging on lung structure and function. The physics-based coupling between multiple scales is a critical step towards a complete integrated physiological model of the human respiratory system: a "virtual human lung."

Modality: In medical imaging, a modality is any of the various types of equipment or probes used to acquire images of the body.

Computed tomography (CT) is a medical imaging method employing tomography where digital geometry processing is used to generate a three-dimensional image of the internals of an object from a large series of two-dimensional X-ray images taken around a single axis of rotation.
'Tomography' is imaging by sections or sectioning.

Confocal laser scanning microscopy (CLSM or LSCM) is a valuable tool for obtaining high resolution images and 3-D reconstructions. The key feature of confocal microscopy is its ability to produce blur-free images of thick specimens at various depths. Images are taken point-by-point and reconstructed with a computer, rather than projected through an eyepiece. 

Disease Focus

Lung-related Disease 

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Scales Examined 

Time Scales

• Microsecond (μs)
• Millisecond (ms)
• Second (s)
• Minutes
• Hours
• Days

Biological Scales

• Molecular
• Molecular Complexes
• Sub-Cellular
• Cellular
• Multi-Cellular Systems
• Tissue
• Organ
• Organ Systems

Length Scales 

• Micrometer (μm)
• Millimeter (mm)
• Centimeter (cm)

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Biomedical, Biological and Behavioral (BBB) Areas and Percent Focus

50% - Lung structure and function, Gas and particulate toxicity, Effects of aging on lung structure and function, anf effects of lung damage.
 

Modeling Methods and Tools (MMT)Areas and Percent Focus

50% - Integration of simulation data across dimensions and scales, Multiphase CFD, statistical representation of respiratory units, quasi-1D modeling of geometric, diffusion, deposition in the lower bronchi, software engineering and integration, HRCT, Micro-CT and CLSM technologies including postprocessing, Geometric/Topological Monte Carlo for coupling micro-CT/CLSM to Q1D functional models.  

Software Development