Hyperpolarized Nuclei for NMR Imaging and Spectroscopy – Methodology and model studies of lung and vascular function

Sammanfattning: Based on the principle of nuclear magnetic resonance (NMR), magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are widely used methods in medical diagnostic imaging and biological research. Clinical MRI has been restricted to imaging of protons, for reasons of sensitivity. In recent years, hyperpolarization techniques have emerged that can increase the NMR signal by 5–6 orders of magnitude. The increased signal from hyperpolarized substances enables investigation of non-proton nuclei, and thus makes novel kinds of examinations possible, e.g., imaging of the lungs and respiratory airways after inhalation of hyperpolarized gas. In this work, applications related to vascular imaging and lung function were investigated, using three hyperpolarized nuclei: 129Xe, 13C, and 3He. In addition, practical aspects regarding the handling and utilization of hyperpolarized substances were evaluated. The potential of angiography using echo-planar imaging (EPI) was investigated using dissolved 129Xe in a phantom model. Long relaxation times were achieved in the in vitro experiments, allowing images of reasonable quality to be acquired within a scan time of 44 ms. Under in vivo conditions, severe limitations are expected, which are mainly due to short transverse relaxation times. A novel 13C substance with favorable properties for angiography was investigated using an optimized true fast imaging with steady-state precession (trueFISP) pulse sequence. Long relaxation times were obtained also under in vivo conditions (T1 ~ 40 s, T2 ~ 2 s), which permitted the acquisition of angiograms in live rats with a signal-to-noise ratio (SNR) as high as ~500. To investigate regional pulmonary ventilation, a technique was developed in an initial study, that was based on inhalation of 3He gas. A quantitative measurement of gas replacement was calculated from the signal buildup after repeated inspirations of 3He. The relative replacement of gas was close to 1 in the trachea and the major airways, and decreased to ~0.15 in the most peripheral parts of the lung. In a second study, regional ventilation was found to be increased in the inferior parts of the lung as compared with the superior parts, with the subject in supine position, whereas a uniform ventilation was measured in prone position. From measurements of the dynamic uptake of 129Xe from the alveolar gas spaces to the pulmonary blood vessels, several physiological parameters could be derived, including the thickness of the respiratory membrane and the pulmonary perfusion. The method was employed to compare healthy control animals with animals with inflammatory lung injury. A significantly increased membrane thickness (10.0 µm vs. 8.6 µm) was measured in the latter group, whereas the pulmonary perfusion remained unaltered. By using hyperpolarized substances, novel possibilities of gaining physiological information arise, which may comple-ment existing MRI and MRS techniques.