Quantitative Assessment Of Pulmonary Function With Hyperpolarized ¹²⁹Xe Magnetic Resonance

The nuclear spin polarization of ¹²⁹Xe could be enhanced by four orders of magnitude using the technique of spin-exchange optical pumping,also called hyperpolarization,which makes pulmonary gas magnetic resonance imaging(MRI)possible.Because of the good solubility and chemical shift sensitivity to the surrounding environment,¹²⁹Xe gas MRI has unique advantages in quantitatively evaluating pulmonary ventilation,microstructure,and gas exchange function,which cannot be obtained non-invasively by the current clinical imaging modalities.In the last decades,more and more studies reported the applications of hyperpolarized ¹²⁹Xe magnetic resonance(MR)in the diagnosis of pulmonary diseases such as chronic obstructive pulmonary diseases and radiation-induced lung injury.In these studies,researchers tried to demonstrate the feasibility of hyperpolarized ¹²⁹Xe MR in diagnosing lung diseases in the early stage,and many new techniques and application strategies were developed to accurately and quantitatively measure the pulmonary physiological parameters.In this work,a home-built experimental platform for small animal hyperpolarized ¹²⁹Xe gas MRI was built and optimized,and pulmonary function changes were quantitatively evaluated in lung disease models of rats using hyperpolarized ¹²⁹Xe MR.Additionally,a new method for pulmonary function visualization using hyperpolarized¹²⁹Xe MR was proposed.Our studies would be helpful for the clinical promotion of hyperpolarized ¹²⁹Xe MR,and the main results are as follows:(1)The hardwares for small animal hyperpolarized ¹²⁹Xe MRI were built and optimized.¹²⁹Xe MR coils for rats were designed and realized.Additionally,¹²⁹Xe polarizer and hyperpolarized gas delivery system were optimized and upgraded,and the polarization of hyperpolarized ¹²⁹Xe gas was about 20%,which was about twice as high as before.Based on these hardwares,high-resolution gas MR images in rats were acquired.(2)Lung injury caused by fine particulate matter(PM_2.5)was quantitatively studied.Lung injury induced by PM_2.5 could not be evaluated in vivo using current clinical techniques.By using hyperpolarized ¹²⁹Xe MR,we found the thickening of the alveolar septal thickness and the significant differences between the PM_2.5 and healthy rats.Our studies demonstrated the validity of hyperpolarized ¹²⁹Xe MR in evaluating the lung injury induced by PM_2.5 in vivo for the first time,and also indicated hyperpolarized ¹²⁹Xe magnetic resonance spectroscopy(MRS)was more sensitive to the lung injury caused by PM_2.5 than¹²⁹Xe diffusion-weighted imaging(DWI)and pulmonary function tests(PFTs).These methods were also used in subsequent lung disease studies.(3)The progression of acute lung injury(ALI)induced by lipopolysaccharide(LPS)was quantitatively evaluated.Based on the technique of hyperpolarized ¹²⁹Xe MRS,the progress of gas exchange function from deterioration to recovery in 2 to 14 days after LPS instillation was monitored,and the measured physiological parameters in vivo using ¹²⁹Xe MR were consistent with that via lung histological.Although the results of PFTs showed similar trends with hyperpolarized ¹²⁹Xe MRS,no significant difference could be found between the groups in the early stage of the disease.In a word,our results indicated that hyperpolarized ¹²⁹Xe MR was more sensitive to the ALI,which would be helpful for making the ionizing radiation-free and sensitive monitoring of ALI in clinic possible.(4)A method for quantitatively evaluating lung compliance using hyperpolarized ¹²⁹Xe ventilation imaging was proposed.Lung compliance is an important physiological indicator of lung elasticity and cannot be regionally assessed.In the proposed method,lung compliance could be assessed globally and regionally,and the measured global lung compliance via hyperpolarized ¹²⁹Xe MRI showed a good correlation with that obtained by PFTs.By analyzing the measured regional lung compliance,we found the direction-dependence of lung compliance and its changes in lung fibrosis for the first time.Additionally,we also found lung compliance had a good correlation with the microstructure parameters obtained using hyperpolarized ¹²⁹Xe DWI,which indicated lung compliance changes may be caused by the morphological changes of alveoli.In summary,the home-built hyperpolarized ¹²⁹Xe MR experimental platform was built and optimized,on which the feasibility of hyperpolarized ¹²⁹Xe in assessing the PM_2.5induced lung injury and monitoring the progress of ALI was investigated.Additionally,a new method for lung compliance evaluation using hyperpolarized ¹²⁹Xe ventilation imaging was proposed.These results indicated hyperpolarized ¹²⁹Xe MR had unique advantages in diagnosing early-stage lung diseases and in evaluating the lung function regionally,which made it a promising method in pulmonary disease diagnosis in clinic in the future.