Research On Brain Iron Using Quantitative Susceptibility Mapping With Application To The MPTP Mouse Model Of Parkinson's Disease

Parkinson's disease(PD)is a common neurodegenerative disease for the elderly.According to data,the prevalence rate of over 65 years old in China is about 1.7%and this rate has been rising with the aging of population.At present,the mechanism,accurate diagnosis and effective treatment still remain unknown.In recent years,more and more studies have shown that there is excess iron deposition in the substantia nigra(SN)of PD patients.The accuracy and sensitivity of quantitative susceptibility mapping(QSM)for cerebral iron quantification are so high that the susceptibility was found to be significantly higher in the SN of PD than in healthy controls in many researches.But the application of QSM in the PD mouse model has not been reported.In this research,QSM was used to measure cerebral iron deposition change in MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahy-dropyridine)mouse model,a kind of PD animal model,providing a quantitative index for further study of PD using mouse model.In the first part of this research,we proposed a method for QSM reconstruction,Improved Morphology Enabled Dipole Inversion(iMEDI),which further introduced edges constraints based on prior information except the total variation constraint in smooth regions.Compared to MEDI method in numerical simulation,gadolinium phantom and in vivo data,the proposed method not only reduced root mean square errors(RMSE)and high frequency error norm(HFEN),but also improved determination coefficient(R2)and structural similarity(SSIM).The streaking artifacts near edges was effectively suppressed by the prior information in the proposed method.Then In the second part,QSM was validated by phantoms,including two kinds of iron solution,superparamagnetic iron oxide(SPIO)and ferric chloride(FeCl3).Each phantom contains five kinds of concentrations.The goodness of fitting between solution concentrations and measured susceptibility is 0.9810(SPIO)and 0.9806(FeCl3),which demonstrates that QSM can measure the iron content accurately.Finally,QSM was used to measure iron deposition change in mice treated with MPTP,a kind of PD animal model.The susceptibility was found to be significantly(P<0.05)higher in the substantia nigra(SN)and striatum of MPTP model mice(n = 5)than in controls(n = 5):for SN,7,90±0.86 ppb VS 4.72± 1.48 ppb(in vivo)and 5.92±0.84 ppb VS 3.92 ± 0.67 ppb(ex vivo);for striatum,4.00 ± 0.79 ppb VS 2.38 ± 0.44 ppb(in vivo)and 3.41 ±0.61 ppb VS 2.29±0.35 ppb(ex vivo).Meanwhile,prussian blue staining also found iron deposition in the MPTP model mice.Additionally,a negative correlation was found between the time in the mice stayed on the rod,measured by rotarod behavior experiment,and the susceptibility of the SN(in vivo:R =-0.81,P=0.004;ex vivo:R =-0.67,P = 0.04)and the striatum(in vivo:R =-0.79,P = 0.006;ex vivo:R =-0.71,P = 0.02).QSM is advantage for iron quantification,and susceptibility can be a useful biomarker for studying PD in future.