Application Of Hyperpolarized ¹²⁹Xe Diffusion MRI For Visual Detection Of COPD

Magnetic resonance imaging（MRI）is a method with wide application for clinical medical imaging in vivo,noninvasively and without ionizing radiation,which has many advantages,i.e.,high resolution and tissue penetration,high imaging contrast for soft-tissue and multi-parameters imaging modalities.However,the signal of the traditional MRI is from the proton of water in the body and the lung contains a lot of airspace.Therefore,the traditional MRI is unsuitable for lung imaging due to its low proton density.Chronic obstructive pulmonary disease（COPD）has high morbidity and mortality,which always affects the life quality of humans and burden the social economy.All over the world,there are 70%COPD patients in China.The primary induced reason for COPD is tobacco smoke.The typical pathological features of COPD are chronic bronchitis and emphysema.But at present the way for the diagnosis of COPD is poor and the traditional diagnosis method mainly including pulmonary function tests（PFTs）and X-ray computer tomography（CT）cannot detect the change of microstructure of lung sensitively.In the recent decades,the hyperpolarized（HP）gas(3He or ¹²⁹Xe)pulmonary MRI has been developed to visualize the lung in vivo as a suitable method,including pulmonary structure imaging or function detection,i.e.,pulmonary ventilation,pulmonary microstructure in the acinar level,pulmonary oxygen partial pressure and gas exchange.The HP gas diffusion in the lung is restricted and highly related with the microstructure,based on which the diffusion MRI of HP gas has been developed and demonstrated very sensitive to detect the change of pulmonary microstructure.The usual gas for the studies are 3He and ¹²⁹Xe.The 3He is very expensive due to the limited reserves on earth and application for military areas,which has bad application prospect.Therefore,in the dissertation,we focused on the corresponding animal study about the application of HP ¹²⁹Xe diffusion MRI for visual detection of COPD.Firstly,the animal experimental platform for HP ¹²⁹Xe pulmonary MRI based on 7 T MRI was built.Then the following four part experiment studies were developed,Firstly,the HP ¹²⁹Xe pulmonary diffusion MRI with a single b value was used to visually detect the COPD rats.The results suggest the apparent diffusion coefficient（ADC）distribution of HP ¹²⁹Xe in the lung could been obtained in the experiment.The mean ADC value in the COPD group increased significantly compared with that in the control group and the distribution of ADC values in the lung was found a little broaden in the COPD group.The results were consistent with those from histological sections of vitro lungs.Secondly,multi-b pulmonary diffusion MRI of HP ¹²⁹Xe was used to quantify the lung respiratory airways and further detect the rats with mild emphysema.The results suggested the corresponding morphologic parameters including the outer radius（R）,the inter radius（r）,alveolar sleeve depth（h）and so on could been measured in vivo by the HP ¹²⁹Xe diffusion MRI,which was consistent to those reported by previous studies.Especially the alveolus surface to volume ratio（S/V）in the rat lungs were first measured by the method.Further,the measured parameters including DL（longitudinal diffusion coefficient）,r,h and S/V in the mild emphysematous rats exhibited a significant difference with those in the control group（P<0.05）,which were consistent with those from histology.Meanwhile,the study suggested that the hyperpolarized ¹²⁹Xe DL was more sensitive than DT（transverse diffusion coefficient）to detect mild emphysema.Thirdly,the diffusional kurtosis imaging（DKI）was firstly used to describe the HP ¹²⁹Xe diffusion in the rat lungs and further used to detect the lung lesions induced by smoking.The results suggested the decay of HP ¹²⁹Xe signal with increasing b values deviated from a mono-exponential decay,which meant the diffusion of HP ¹²⁹Xe in the lung was non-Gaussianity.The DKI model was demonstrated very suitable for the fitting of signal vs b values.Further,the extracted parameters from HP ¹²⁹Xe pulmonary DKI including the Dapp and Kapp exhibited significant difference in the smoking rats compared to the control group（P<0.05）.It could be deduced according to the corresponding results that the DKI not only could be used to detect the change of alveolar,but also probably related with the disease of small airways.At last,a novel flip angle scheme was proposed,named combination of variable and constant flip angle（CVCFA）,for the HP gas pulmonary diffusion MRI.Due to the non-recovery longitudinal magnetization after RF exciting for HP gas,at present the modified schemes mainly including variable flip angle（VFA）and interleaved constant flip angle（ICFA）were usually used for HP gas diffusion MRI.The CVCFA scheme combined the two methods.The results from computer simulation and experiments in vivo suggested that for the HP gas diffusion MRI,the VFA scheme could promise the accuracy of diffusional signal fitting vs multi-b,but the SNR of multi-b images was low.In contrast,the ICFA scheme could improve the multi-b images SNR,but the bias for the fitting of diffusional signal vs b values still existed.The CVCFA scheme combined the advantages of the VFA and ICFA schemes,which was demonstrated to not only promise the image SNR,but also improve the accuracy for the fitting of diffusional signal vs b values and more suitable for HP gas pulmonary diffusion MRI.