Hyperpolarized 3He-diffusion MRI in evaluation of lung structure in emphysema. Validation and development of the method

University dissertation from Department of Diagnostic Radiology, Lund University

Abstract: Abstract
COPD is a major cause of chronic morbidity and mortality throughout the world. It is a preventable and treatable disease. Smoking is the most commonly encountered risk factor for COPD and the habit now unfortunately starts at earlier ages than before. There is a strong necessity to diagnose COPD in early stages before symptoms present themselves. MRI with hyperpolarized 3He using diffusion weighted sequences has the potential to detect and quantify parenchyma destruction in emphysema, the main manifestation of COPD.
Study I investigated the short-term reproducibility of the method and the volume of gas required to obtain suitable results in normal volunteers and patients with COPD. The mean ADC measurement was highly reproducible, sensitive to small differences in alveolar size and clearly separated volunteers and patients. There was a dependency of inhaled volume.
Study II investigated the long-term reproducibility, age-dependency and anatomical variation of ADC in normal volunteers. The mean ADC measurement was highly reproducible over one year. There was correlation between age and mean ADC. There was a difference in mean ADC between anterior and posterior parts of the lungs in supine position probably depending on the gravity.
Study III compared hyperpolarized 3He-diffusion MRI technique with MSCT and different PFT:s. The mean ADC correlated well with emphysema index and 15th percentile from CT. DL,CO is the PFT best correlating with emphysema grade and the correlation was higher between 3He -MRI and DL,CO than between CT and DL,CO.
Study IV investigated if hyperpolarized 3He-diffusion MRI technique was sensitive enough to detect emphysema progress over a year. The mean ADC did not detect changes over 12 months. An ad hoc analysis performed afterwards using a textural analysis, lacunarity analysis, showed progress in patients with COPD who smoked at the beginning of the study, but not in patients who had stopped smoking earlier.
In conclusion, hyperpolarized 3He-diffusion MRI technique is a robust method, highly reproducible over a short and a longer period of time. The method has been validated with standard methods, pulmonary function tests and CT. The combination of MRI, hyperpolarized gases, and a proper textural analysis of the data will likely provide a powerful investigative tool at least in research settings for understanding the pathophysiology of emphysema and evaluation of therapies designed to alter the course of disease even if economic obstacles may prohibit a more widespread clinical use.