ABSTRACT
I. Introduction 303
II. Background 304
A. Overview of Lung Structure 304
B. Techniques for Measuring the Diffusion of 3He 305
GRE Pulse Sequences with Bipolar Gradients 305
Spin-Echo Train Pulse Sequences 308
Magnetic Tag Dissolution 309
C. Quantitative Models of Diffusion in the Lung 310
Spherical Shells 311
Isotropically Distributed Cylinders 311
The Lung as a Porous Medium 312
III. ADC Measurements in Human Subjects 313
A. Studies in Healthy and Diseased Subjects 313
B. Time Dependence 315
C. Directional Dependence 317
D. Dependence on Lung Inflation 319
E. Model-Based Diffusion Results 320
IV. Conclusion 321
References 322
I. Introduction
Since the emergence of hyperpolarized 3He gas as a novel contrast agent for MRI,
there has been substantial interest in exploiting the unique properties of this gas
for evaluating lung structure and function. Of particular relevance for assessing
the microstructure of the lung, 3He has a very high self-diffusion coefficient
(2 cm2/s at body temperature and a pressure of 760 Torr) which, in an unrestricted environment, results in relatively large diffusion-driven displacements of 3He atoms during time periods of relevance for MRI, such as during the echo
time of a gradient-echo (GRE) pulse sequence, as routinely used for hyperpol-
arized 3He imaging. For example, within air in an unrestricted space, the root
mean squared displacement of a 3He atom is 2 mm during 5 ms. A second important characteristic of 3He is its low tissue solubility, which
effectively confines inhaled 3He gas to the airspaces of the lung. When 3He is
confined to relatively small spaces such as the distal airway structures, which
have characteristic lengths on the order of 0.1 mm, its motion is restricted result-
ing in reduced displacements and a decrease in the apparent diffusion coefficient
(ADC) as measured by MRI (1-4). Depending on the parameters of the pulse
sequence, these ADC values may exhibit a complex dependence on a variety
of morphological features of the lung microstructure including the surface-to-
volume ratio, the length scales of the distal airways, the anisotropy of airway
orientation, and the tortuosity of airway connectivity. Application of diffusion
MRI methods to hyperpolarized 3He thus presents the opportunity to create
image contrast on the basis of differences in the morphology of the microstruc-
tural environment between each voxel in the image, yielding a powerful tool
to quantitatively evaluate disease processes that alter the underlying structure
of the lung.
