A Chemical Exchange Saturation Transfer Imaging Study Of Parkinson's Disease At 7 T

Parkinson's disease(PD)is the second most common neurological disorder of central nervous system with unknown etiology.The most obvious symptoms of PD in early stage are shaking,rigidity,dyskinesia while the loss of dopaminergic neurons in subtantia nigra(SN)and the presence of Lewy bodies are the main pathological characteristics.So far,the diagnosis of PD mainly depends on medical history and neurological tests,but one major drawback comes from the subjectiveness of physicians which relies heavily on clinical experience.Moreover,the diagnostic accuracy of early-staged PD is poor.Therefore,a biomarker to objectively evaluate PD plays a key role to the determination and therapeutic effect of treatment.In our study,we applied Chemical Exchange Saturation Transfer(CEST)imaging on MPTP-induced Parkinson's disease mice,and compared MTRasym based on the analysis of Z-spectrum asymmetry and the MTRrex,AREX which derived from the combinations of 5-pool Lorentz fitting and inverse Z-spectrum analysis,and evaluated the performance of different CEST quantification methods.The first part of our study exploited different CEST quantification(CSET signal at 2 ppm)methods to evaluate the changes in SN of PD mice.This experiment required 12 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced acute PD mice as experimental group and 6 normal mice as control group,which were scanned using routine MRI and CEST sequences and then the data were processed by self-written MATLAB software.Relaxation time(T,,T2)and magnetization transfer ratio(MTRaym,MTRrex and AREX)were calculated.The results told that there was no significant difference in T1,T2 and MTRasym of the SN,hippocampus and cortex between control group and experiment group,and alterations of significance were found in MTRre,and AREX of SN.In conclusion,the quantification derived from the combination of 5-pool Lorentz fitting and inverse Z-spectrum analysis was more sensitive in indicating the changes in SN of PD than the common quantification based on Z-spectrum asymmetry.In the second part,we studied the quantification of striatum in acute and subchronic PD mice by GluCEST(CEST signal at 3 ppm).MPTP-induced acute and subchronic(n = 6 respectively)as well as 6 control group mice were scanned with routine MRI and CEST sequence and the T1,T2 and several magnetization transfer ratio including MTRasym,MTRre,and AREX,were calculated.The results showed an significant increase in MTRasym at high B1 and AREX at lower B1 between subchronic PD group and control group while the relaxation time of T,and T2 indicated no significant alterations while no significant alterations were found between acute PD and control group.It told that the rise of glutamate level in striatum of MPTP-induced PD mice can be detected by GluCEST and MTR based on the combination of inverse Z-spectrum analysis and 5-pool Lorentz fitting is more sensitive.In conclusions,we found that changes in SN and striatum of MPTP-induced mice can be detected by CEST,and quantifications derived from combination of multiple pools and inverse Z-spectrum analysis performed better than Z-spectrum asymmetry quantifying.