Quantitative Assessment of Lung Microstructure in Healthy Mice Using an MR-based 3He Lung Morphometry Technique

Recently developed in our laboratory the MRI-based technique - 3He Lung Morphometry - is a unique tool allowing in vivo measurements of lung microstructural parameters such as alveolar volume, surface-to-volume ratio and alveolar density. These parameters are commonly used by lung physiologists and pathologists but were previously available only from invasive biopsy studies. 3He Lung Morphometry was originally developed for human studies but there is a need to expand it for studies of small animals like mice and rats that are used to advance our knowledge of lung physiology in health and disease and for development of drugs. Such an expansion of the 3He Lung Morphometry technique is the subject of this dissertation. To achieve this goal we have developed a theory of 3He gas diffusion in lung airways and alveoli and tested this theory in two distinct experiments. In the first experiment, using a Stejskal-Tanner method, we examine the diffusion of 3He atoms as it occurs in tiny airways of mouse lungs. Through a series of magnetic resonance: MR) measurements we study the pattern of signal decay over very short periods of time. This decay crucially depends on the confining effects of the spins in very small compartments, lung acinar airways and alveoli. The signal decay is mathematically modeled after the theory developed in our laboratory that describes 3He gas diffusion in the compartments that are at the scale of mouse lung airways: ~100 µm). Applying our MR diffusion decay measurements in the mouse lung mathematical model allowed us to provide close estimation of lung microstructural parameters at the alveolar level. The values obtained for those parameters are in agreement with various histological findings published in the literature, as well as our own histological findings. These values are also in agreement with an in vivo mouse lung 3He MR experiment also conducted in our laboratory. Our theory of 3He gas diffusion in lungs relies on an assumption that diffusion in the lung acinar airways is anisotropic. Thus, a set of experiments were performed to demonstrate that the gas diffusion in mouse lungs is indeed anisotropic. The MR measurements that demonstrate anisotropy of the 3He gas diffusion in mouse lung also use a series of MR diffusion measurements. These MR measurements are directionally interrelated in such a way that the results unequivocally demonstrate diffusion anisotropy, one of the founding assumptions for our mathematical mouse lung model. These two studies examined healthy lungs and allowed us to develop a robust and reliable tool to measure mouse lung parameters. We applied this tool and provided the first in vivo measurements of changes in lung microstructure that occur as a result of smoking.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Electrical and Systems Engineering

Year dc:date.available

2011

Author dc:creator

• Osmanagic, Emir

Contributors dc:contributor

• Martin Arthur

• Biomedical engineering
• Electrical engineering
• Nuclear physics
• 3He
• Hyperpolarized gas
• Lung Microstructure
• Morphometry
• Mouse
• MRI

Language dc:language

English (en)

DOI

https://doi.org/10.7936/K7CZ3566

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:etd-1628