PEGylated Superparamagnetic Iron Oxide Nanocrystal As MRI T1-T2 Dual-Modal Contrast Agent For Rat Liver Fibrosis Stage

Objective:To investigate the diagnosis and discrimination ability of small size PEGylated superparamagnetic iron oxide(SPIO@PEG)among different stages of biliary liver fibrosis in rat model as a T1-T2 dual-modal magnetic resonance imaging(MRI)contrast agent.Methods:In this paper,themonodispersedsmall size SPIO@PEG nanoparticles as T1-T2 dual-modal MR contrast agent,and its physical characterization,magnetic resonance performance and biosecurity were analyzed.3,5-diethoxycarbonyl-1,4-dihydro-collidine(DDC)included biliaryfibrotic modal was builtin this study.At 1,4,8 and 12 weeks after starting modeling,MR imaging was carried out for each rat,and the fibrosis stage was determined by taking pathological results of rat liver after the MR scans.For MR scans,we used conventional T1and T2 weighted imaging,as well as T1 and T2mapping to quantitatively measure the contrast to noisy ratio(CNR)and the T1,T2relaxation time in pre-and post-SPIO@PEGcontrasted enhancement images.Finally,the intelligent decision analysis method of image fusion of T1 and T2mapping before and after SPIO@PEG enhancement was studied by MATLAB,and the positive pixel ratio(PPR)of the liver was calculated to test the distinguish ability of stages of liver fibrosis.Results:the average size of SPIO@PEG nanoparticleswere tested by transmission electron microscope(TEM)and dynamic light scattering(DLS).And the results are 5.21±0.07nm and 6.86±2.99nm.TheFourier transform infrared spectrometer(FTIR)showed a characteristic peak(1111.67cm-1)of PEG at SPIO@PEG.At the different magnetic field of 0.5T,1.5T and 3.0T,the relaxation rateof T1(r1)were 22.7mM-1s-1,16.0 mM-1s-1and 12.9 mM-1s-1,and the relaxation rateof T2(r2)were 39.6mM-1s-1,41.7mM-1s-1 and 45.2mM-1s-1respectively.The r2/rlwere 3.51 at 3.0T。We found that ΔCNR-T1 increased with the progression of liver fibrosis.On the contrary,ΔCNR-T2were decreased.T1 and T2 relaxation time were both upgrade with the progression of liver fibrosis.However,all these parameters mentioned before could notaccurately distinguish the stages(S0-S4 stage)of hepatic fibrosis rats.Thecombination of ΔT1%and ΔT2%was capable to distinguish the stages ofliver fibrosis,but it cannot independently differentialthe severe stages of liver fibrosis.Finally,according to the image fusion results,the T1 and T2 dual-modal fusion parameterPPR showed good correlation with the stages of liver fibrosis(r=0.979)and reached statistical difference in all the different stages of liver fibrosis(P<0.05).Conclusion:SPIO@PEG nanoparticles successfullysynthesized and exhibited good T1 and T2 relaxation efficacy and biosafety.T1 and T2dual modal image fusion parameters PPR based on MATLAB couldaccurately diagnose and distinguish the different stages of biliary hepatic fibrosis of rat.And it is hopeful to be areliable method for noninvasively monitoring the progression of hepatic fibrosis and the response to antifibrosis therapy.