Subtypes Evaluation Of Motor Dysfunction In Parkinson’s Disease Using NM-MRI,DTI And MEGA-PRESS Sequences

Parkinson’s disease(PD)is a heterogeneous neurodegenerative disorder in the elderly,pathologically characterized by the loss dopaminergic neurons in the substantia nigra pars compacta(SNc)and dopaminergic dysfunction in striatum.This heterogeneity is consistent with the existence of motor subtypes,empirically divided into tremor dominant(TD)and Postural instabilitygait difficulty(PIGD)subtypes,and these subtypes are associated with different disease progression and neuropathological features.MR Imaging is an optical tool for neural diseases:Neuromelanin-sensitive MR Imaging(NM-MRI)has been found to provide notable contrast between the SNc and surrounding brain tissues as a biomarker of the loss dopaminergic neurons for PD;MEGA-PRESS was afford to detect the inhibitory neurotransmitter GABA levels in basal ganglia area;Diffusion tensor MR Imaging(DTI)could tract the dopaminergic projection fibers of nigrostriatal pathway.Although the pathological changes observed in the TD patients differ from those observed in the PIGD patients,the neural mechanism underlying these disparate presentations is still uncertain.The purpose of present study is to elucidate whether differences between PD patients with two different motor subtypes can be characterized by 1)the underlying SN degeneration based on NM-MRI;2)the GABA level alteration based on MEGA-PRESS;3)the nigrostriatal pathway fiber changes based on DTI.So this study was divided into three parts:Part 1 Subtypes Evaluation of Motor Dysfunction in Parkinson’s disease using Neuromelanin-sensitive Magnetic Resonance ImagingParkinson’s disease(PD)is characterized by the loss of neuromelanin(NM)-containing neurons in the substantia nigra pars compacta(SNc),and it is divided into two motor subtypes:the postural instability gait difficulty(PIGD)and the tremor dominant(TD)subtypes.With NM-sensitive Magnetic Resonance Imaging(NM-MRI),investigators have been able to accurately detect signal attenuation in SNc of PD;however,the difference of NM loss between PIGD and TD subtypes is still unclear.Thus,the aim of this study was to evaluate the differences in NM-MRI between PD motor subtypes.PD patients were classified into PIGD(n = 14)and TD groups(n = 9);20 age and sex matched controls were recruited.We compared the signal intensity contrast ratios in medial and lateral regions of the SNc using NM-MRI in PIGD,TD,and controls,respectively.Remarkable signal attenuation was observed in the lateral part of SNc in PD when compared with the controls,and we were able to detect more severe signal attenuation in the medial part of SNc in PIGD patients in comparison with that in the TD group.Also,the medial part of SNc,ipsilateral to the most clinically affected side,showed the highest power to discriminate the PD motor subtypes(AUC,81%;sensitivity,71.4%;specificity,77.8%).Our results indicated a potential diagnostic value of NM-MRI to discriminate the PD motor subtypes,providing new evidence for the neuropathology-based differences between the two subtypes.Part 2 Inhibitory motor dysfunction in Parkinson’s disease subtypesParkinson’s disease(PD)is divided into two motor subtypes:postural instability gait difficulty(PIGD)and tremor-dominant(TD)subtypes.Increasing evidence has suggested that the GABAergic neurotransmitter system is involved in the pathogenesis of PD;however,to-date,MRS of GABA in PIGD and TD subtypes has not been performed.Thus,the aim of this study was to evaluate the differences between PD motor subtypes of GABA levels using MEGA-PRESS.PD patients were classified into PIGD(n = 13)and TD groups(n = 9);sixteen age-and gender-matched healthy controls were recruited(Table 1).All subjects were right-handed and underwent 3 T MRS scan including MEGA-PRESS.GABA+ levels and Creatine(Cr)levels were quantified in the left basal ganglia(BG)using Gannet.Segmentation of T1-weighted images using SPM8 was also performed(Fig.1-2).Differences in GABA(?)+ levels among three groups were analyzed using analysis of covariance(ANCOVA).The sensitivity,specificity,and accuracy of BG GABA levels for differentiating PIGD and TD were calculated.The relationship between GABA levels and unified Parkinson’s disease rating scale(UPDRS)was also analyzed.GABA+levels were significantly lower in left BG regions of PD patients compared with healthy controls(p<0.001).In PD patients,the GABA concentration was lower in the TD group than PIGD group(p = 0.025).Cr levels in PIGD and TD were lower than controls(p = 0.006;p = 0.001).No differences in voxel segmentation were observed.The sensitivity,specificity,and accuracy of BG GABA levels for differentiating PIGD and TD were 61.5%,88.9%and 80.3%respectively.A significant negative correlation was found in PIGD between GABA levels and UPDRS(r =-0.586,p = 0.035),while no correlation was found in TD.Low BG GABA levels in PD patients,and differences between PIGD/TD patients,suggest that GABAergic dysfunction may play an important role in the pathogenesis of Parkinson’s disease.Part 3 Subtypes evaluation of motor dysfunction in Parkinson’s disease using diffusion tensor MR ImagingPurpose:Nigrostriatal pathway that connects the substantia nigra pars compacta with the dorsal striatum,is the primary dopamine pathway in the brian.The nigrostriatal pathway is involved in the production of movement and is related with Parkinson’s disease(PD).Diffusion tensor MR Imaging(DTI)uses diffusion tensor data and allows visualization of specific white matter projection fibers.So this study was aimed to evaluate the alteration of nigrostriatal pathway fibers in PD and different motor subtypes using DTI.Materials and methods:Forty PD patients(24 PIGD,16TD)and 20 age-and sex-matched healthy controls were recruited in this study.All subjects underwent an MRI scan including DTI at 3.0T scanner.The acquired DTI data was preprocessed with spm8,and then traced the whole brain fibers using user-friendly DTItoolkit,visualized the specific nigrostriatal dopaminergic projection fibers under TrackVis software.DTI parameters of fractional anisotropy(FA),mean,radial,axial diffusivity(MD,RD and AD),and track count of nigrostriatal pathway were measured.The DTI parameters in PIGD,TD and controls were compared with ANOVA and Bonferroni analysis.Results:The nigrostriatal pathway tract in the PD patients was sparser than that in the healthy controls,especially in TD subtype of PD.The tract count value was different between PIGD and TD subtypes.The DTI parameters of nigrostriatal fibers also altered in PD patients compared with controls:FA was decreased;MD/AD/RD was increased.There were significant differences in DTI parameters of nigrostriatal pathway between PIGD and TD patients.Conclution:DTI tractography indicated that the nigrostriatal pathway dopaminergic projection fibers were involved in PD patients,furtherly,DTI parameters were different between PIGD and TD subtypes.Nigrostriatal pathway DTI may be a valuable tool in clinical practice and for future research in PD,contributing to a better understanding of clinical and pathological heterogeneous characteristics of PD.