Quantitative Studies Of The Pulmonary Structure And Function In Humans With Hyperpolarized ¹²⁹Xe Magnetic Resonance

Clinical magnetic resonance(MR)imaging of the lung airspace is challenging due to the lung's low proton density and the inhomogeneous magnetic environment within the lung created by numerous tissue-air interfaces.The spin-exchange optical pxunping(SEOP)technology could increase the 129Xe nuclear polarization by four to five orders of magnitude(hyperpolarized 129Xe)higher than the corresponding thermal equilibrium state.Thus,MR imaging(MRI)using hyperpolarized 129Xe provides unique strategies for evaluating pulmonary structure and function.Recently,pulmonary disease has become a serious health problem.There are 99.9 million chronic obstructive pulmonary disease(COPD)patients and about one-third of the world's total smokers in China.In this study,the pulmonary structure and function of the human lung was quantitatively evaluated with hyperpolarized 129Xe MR.The research work includes establishment of the ventilation function measurement with MRI,measurement of the blood-gas exchange function with MR,MR study of the smoke-induced lung injury,measurement of the blood-gas exchange function with MRI and MRI study of the honeycomb model of the pulmonary microstructure.Significant results are shown as follows.Firstly,hyperpolarized 129Xe MRI of the pulmonary ventilation function has been realized and the standard procedure has been established.Respiratory devices applied for hiumans have been built;different kinds of data processing methods and software for 129Xe MR spectra have been developed;the pulse sequences for 1.5 T MRI and MR spectroscopy(MRS)have been designed and implemented.Based on these work,the MR parameters of hyperpolarized 129Xe in the human lung were measured,such as the spin-lattice relaxation time constant(Ti),the spin-spin relaxation time constant(T2)and the spin-spin relaxation time constant in inhomogeneous magnetic field(T2*);preliminary studis on the structure and function changes caused by lung diseases,such as COPD,were carried out.Secondly,single breath-hold measurement method of the pulmonary gas exchange and diffusion in humans with hyperpolarized 129Xe MR has been developed and a new parameter,namely,the perfusion factor of the respiratory membrane(SVRa/g),has been proposed.The pulse sequences including chemical shift saturation recovery(CSSR)and diffusion-weighted MRI(DWI)have been designed and implemented and the changes of pulmonary structure and function caused by age and COPD have been studied in healthy younger,age-matched control and COPD subjects.The results showed that SVRd/g was sensitive to the changes of pulmonary structure and function caused by age and COPD and correlated well with the results of the pulmonary function tests(PFTs)and computed tomography(CT)examination.The results indicated it would be useful in the early diagnosis of pulmonary diseases in clinical practice.Thirdly,the cigarette smoke-induced lung injury(SILI)in humans was quantitatively estimated with hyperpolarized '29Xe MR.The influences of different physiological parameters on the signal establishment curve of the dissolved-phase'29Xe were studied on the basis of theoretical simulation,which provided theoretical basis for the studies of the pulmonary blood-gas exchange function.The changes of pulmonary structure and function caused by SILI have been studied in healthy younger,age-matched control and smoking subjects.The results showed that SILI resulted in airflow limitation,microstructure enlargement and lower blood-gas exchange efficiency in humans with long-term smoking history,which provided experimental basis for the clinical detection of SILI.Fourthly,visualization methods of the pulmonary blood-gas exchange function with hyperpolarized 129Xe MRI have been developed.Two direct MRI methods for the dissolved-phase 129Xe,namely,bi-directional asymmetric echo(BASE)and bi-directional asymmetric multi-echo imaging(BAMI),have been developed.The pulse sequence of BAMI and BAMI have been designed and implemented and the feasibility was validated in human subjects.This study provided experimental basis for the visual detection of the pulmonary perfusion function.Finally,an acinar duct model of the human lung,namely,honeycomb model(HV),has been proposed.The influences of the MRI parameters on the measured results were studied on the basis of theoretical simulation.The simulation results showed that lower measurement errors and higher space utilization were found compared to the currently used cylindrical model(CM).The pulse sequence of DWI and balanced-steady state free precession(bSSFP)with 3D compressed sensing(CS)was designed and implemented and the honeycomb model was tested in the healthy and COPD subjects.The experimental results showed that the alveolar surface utilization of HM was higher than CM and the parameter,namely,alveolar surface(Sa),was sensitive to the pulmonary microstructure changes caused by pulmonary diseases.