64-slice CT Perfusion Imaging In Radiation-Induced Lung Injury: Experimental Study

This study was divided into two parts:Part One,to explore the establishment of a rabbit model of radiation-induced lung injury(RILI)and its appreciation via pathohistology;Part Two,to evaluate the feasibility of 64-slice CT perfusion(CTP),and to study the CTP signs and its pathologic basis in rabbit models of RILI.Part One:establishment and appreciation of rabbit models of RILIObjective To establish rabbit models of RILI which were suitable for CT and CTP scanning,so as to provide essential conditions to further study.Materials and methods 48 New Zealand rabbits were randomly classified into two groups,one received 25 Gy with single fraction irradiation in a whole unilateral lung(test group,Group A,n=36)and another received sham-irradiation(control group,Group B, n=12).Each rabbit from Group A and B was sacrificed at the different time points, extracting six specimens from upper,middle and lower fields of bilateral lung,respectively. These specimens were processed for various analyses,including the followings:(1)HE staining of common light microscopy;(2)ultramicrostructures were observed via electron microscopy;(3)cytokine(such as TNF-a,TGF-β1)expression in local lung tissue,was detected by immunohistochemistry.Results(1)Significant histopathological changes were found after irradiation in Group A.At early stage,acute inflammatory reaction dominated,manifesting with exudation, hyperaemia,and pulmonary interstial thickening;at later stage,lung injury was mainly characterized with progressing fibrosis of alveolar septum.Thickness of alveolar wall, density of pulmonary interstitium and amount of fibrocyte from interstitium among subgroups,were significantly different from Group B and had strikingly correlation with post-irradiation time.(2)Those pathohistological changes were confirmed by the results of electron microscopy.The ultimate fibrosis was occurred in Group A,and the amout of collagen fibers increased obviousely along with the irradiation time.(3)In Group A,both TNF-αand TGF-β1 from regional lung tissue,appeared as strong expression,and striking correlation with irradiation time.Conclusion(1)Stable and reliable rabbit models of RILI were made by 25 Gy of high-energy X-rays with single fraction irradiation in a whole unilateral lung.(2) Pulmonary capillary and alveolar epithelium were the main injury parts of RILI. Abnormality of capillary permeability induced by capillary endothelial cells and basement membrane is the core link to the development and degree of RILI.Part Two:Manifestations of 64-slice CTP Imaging and its pathologic basis in rabbit RILIObjective To evaluate the feasibility of 64-slice CT pulmonary perfusion in rabbit models, to seek the value of early monitor and diagnosis in CTP of rabbit RILI,via analyzing the correlation between the alterations of the hemodynamic parameters and pathohistology,as well as the levels of plasmic cytokin,at different postirradiation-time points.Materials and methods 72 healthy New Zealand rabbits were randomly classified into two groups,one received 25 Gy with single fraction irradiation in a whole unilateral lung (test group,Group A,n=48)and another received sham-irradiation(control group,Group B,n=24).Each group was divided into 12 subgroups respectively in accordance with different postirradiation/pseudo-irradiation time points(1,6,12,24,48,72 h and 1,2,4,8, 16,24 w).Each rabbit was performed with HRCT and CTP at every pre- and post-radiation time point,then the whole blood was extracted via cardiac puncture.At last, each rabbit was sacrificed,extracting six specimens from upper,middle and lower fields of bilateral middle lung zone,respectively.An extra lung tissue was obtained according the manifestations of HRCT if there were such abnormal signs.Morphology of specimens was observed using light- and electron microscope,immunohistochemistry;the levels of plasmic TNF-αand TGF-β1 were measured with ELISA after high-speed centrifugalization. The changing regularity of CTP parameters was studied and compared with the above observations in order to find the correlation among them.Results(1)CTP parameter values of pre-irradiation were consistent with Gaussian distribution.W values of rBF,rBV,rTTP,rPS were 0.98419,0.98365,0.98199,0.99745 (P＞0.05),Kappa=0.8563.(2)the changing tendency of CTP parameters from Group A after radiation was significantly different from that of Group B,especially at the time points of 48h～2w.(3)There was a significant correlation between the changes of CTP parameters and pathohistology in irradiation lungs of Group A,e.g.the correlation between rPS and the amounts of RBC outside the blood capillary or the destruction of basement membrane.(4)The detection rate of RILI with CTP was obviously higher than that with HRCT,especially at 1w,8w and 24w.(5)there was no significant correlation between the levels of plasmic TNF-αand TGF-β1 and the expression of regional intrapulmonary TNF-αand TGF-β1 or the increase of capillary permeability.Conclusion(1)high reliability and stability were found in CTP parameters measured in rabbit lungs;(2)CTP parameters,rPS especially,may reflect the pathophysiologic state of different stages of RILI.(3)By the time of detecting RILI,the detection rate of CTP was clearly superior to that of HRCT,especially there is potential value for rPS in predicting RILI.(4)High expression of intrapulmonary TGF-β1 and TNF-αdidn't release as a line pattern,although the capillary permeability increased.Further study should be needed to find the basic reason.