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Non-invasive, regional assessment of lung function has the potential to markedly enhance early diagnosis and management of disease, to accelerate drug discovery and trials, and to provide fundamental insights into lung disease pathogenesis. For the last fifteen year, our group has been involved in developing non-invasive, quantitative polarized gas MRI techniques to meet this need by addressing crucial aspects of both lung structure and function. Our work has included regional measurements of alveolar oxygen tension, ventilation, perfusion, ventilation to perfusion ratio, and apparent diffusion coefficient (a measure of lung microstructure). Although further refinement is necessary, particularly with respect to use with small animals, we believe that the techniques are now sufficiently mature to be applied to important questions surrounding pulmonary disease pathogenesis. Because hyperpolarized (HP) tracer measurements are non-invasive, highly reproducible, and have demonstrated sensitivity to disease, they are ideally suited to answer questions about disease progression. The fact that several aspects of structure and function can be evaluated together, often within the same breath hold, eliminates uncertainties associated with image co-registration and adds to the power of this group of techniques. We are therefore well situated to study regional and chronological relationships between a variety of pulmonary changes, to compare several otherwise hidden aspects of a disease between animal models and with human disease, and measure response to therapy in the same set of subjects. By comparing these measurements to the testable predictions of a disease model we hope to shed light on the root cause of human disease. More recently, we have been involved with polarized 13C technology and its application to metabolic imaging. |
