The Analysis Of Brain Glucose Metabolism And Brain Network With ¹⁸F-FDG PET/CT In Early And Moderate Parkinson’s Disease

Background and ObjectiveParkinson’s disease（PD）is a degenerative disease of the central nervous system in humans.It occurs latently,unilaterally and progresses slowly.The main pathological changes are the damage of dopamine neurons in substantia nigra and striatum.Its clinical symptoms include motor retardation or reduction,stationary tremor,high muscle tone,instability of posture,et al.As the course progresses,the ability of movement in PD patients decreases significantly,and it can be combined with a variety of non-motor symptoms such as olfactory and visual disorders,cognitive decline,depression,constipation or sleep disorders,and so on.Some patients have atypical clinical symptoms or asymptom（subclinical type）,which make diagnosis difficult.There are many similarities between the clinical symptoms of PD and Parkinson’s syndrome caused by various causes,but there are great differences in treatment response and prognosis.At present,the diagnosis and treatment of PD are mainly based on clinical evaluation and follow-up,and there is no clear biomarker to indicate the extent and trend of the lesion.As a result,it is impossible to accurately formulate the treatment plan of PD in time,delay the progression of the disease and improve the prognosis for the clinic.PD affected approximately 1%of the population over the age of 60 years in 2005,and this number is predicted to double by 2030 due to the overall aging of the population all over the world.It seriously threatens the health and life quality of the elderly,reduces the self-care ability and social function of patients,and increases the socio-economic burden by long-term home care inputs.So it is urgent to find effective treatment and prevention strategies for PD.Positron emission tomography/computed tomography（PET/CT）develops fast,which displays the functional and anatomical information meanwhile,reflects the pathophysiological and pathobiochemical processes of PD mainly from the level of tissue,cell and even molecule.Preexisting physiological,biochemical,and metabolic functional changes can be found before the anatomical structure changes.Fluoride[18F]-labeled fluorodeoxyglucose（18F-FDG）is the most commonly used brain glucose metabolic imaging agent in clinical practice currently,which is a glucose analogue,and has a cellular transport process similar to that of glucose,following the basic principles of biological substitution.It can reflect abnormal glucose metabolism of nerve nuclei,which provides a method for the study of brain function in vivo,so as to achieve the purpose of diagnosis and differential diagnosis.The advanced PD patients have more involuntary movements and difficulties in mobility,so they are unable to cooperate with imaging examination.Therefore,this study analyzed and discussed the specific manifestations of the brain regions with relatively abnormal glucose metabolism and brain network topological attributes in early and moderate PD with 18F-FDG PET/CT,and further conducted neural network study based on seed point brain glucose metabolism in each group,as far as possible to accurately diagnose the scope of the brain lesions,imaging characteristics and clinical significance of early and moderate PD.The purpose of this study was to evaluate the value of 18F-FDG PET/CT examination’s sensitivity and specificity in the diagnosis of early and moderate PD,and to provide theoretical basis for more effective diagnosis and treatment of PD.Materials and Methods1 PD patients were enrolled according to the clinical diagnostic criteria based on the brain bank of PD association,London,UK.Only the early and moderate cases with Hoehn-Yahr grade 0-3 were analyzed（see Chapter 1 for details）.Exclusion criteria included patients with histories of other serious medical conditions（see Chapter 1 for details）.According to the above criteria,40 patients with early PD,40 patients with moderate PD（including one excluded patient from the experiment,whose image could not be post-processed because of head movement）and 40 normal controls,who underwent brain 18F-FDG PET/CT examination,were selected for this study.2 Statistical analyses2.1 Statistical analyses of demographic information and clinical data were performed using statistical product and service solutions version 19.0（SPSS 19.0）analysis of variance（ANOVA）,t test,P<0.05 was considered statistically significant.2.2 The brain 18F-FDG PET/CT images of early,moderate PD groups and normal control group were preprocessed with matrix laboratory version R2016a（Matlab R2016a）and statistical parametric mapping version 12.0（SPM 12.0）.Then the generalized linear model was used to construct single factor ANOVA,P<0.05,k>50 voxels was used as the significance threshold.The family wise error（FWE）was used to check,P<0.05.2.3 The 18F-FDG PET/CT images of early,moderate PD groups and normal control group were preprocessed,then the automated anatomical labeling template（AAL,Tzourio-Mazoyer et al.2002）was adopted to extract the standardized uptake value（SUV）of 90 brain regions,and the pearson correlation coefficient of SUV in two brain regions was calculated respectively to obtain the brain functional network and topological attributes（P<0.05）.Nonparametric permutation test was preformed 1000 times,FWE was used to check,P<0.05 was considered statistically significant differences between groups.Results1 Comparative analysis results of glucose metabolism images in early and m oderate PD groups with 18F-FDG PET/CT1.1 Compared with normal control group,the brain regions with relatively a bnormal 18F-FDG metabolism in early PD group:The brain regions with relative h ypermetabolism were bilateral asymmetric thalamus,lentiform nucleus,and pons,etc.The brain regions with relative hypometabolism were bilateral asymmetric parts of fr ontal,temporal,occipital cortex,etc.1.2 Compared with normal control group,the brain regions with relatively abnormal 18F-FDG metabolism in moderate PD group:The brain regions with relative hypermetabolism were putamen_r,thalamus_r,bilateral asymmetric claustrum,etc.The brain regions with relative hypometabolism were bilateral asymmetric parts of occipital lobe,insula_r and other cortical areas.1.3 Compared with early PD group,the brain regions with relatively abnormal 18F-FDG metabolism in moderate PD group:The brain regions with relative hypermetabolism were thalamus_r,lentiform_nucleus_r,part of frontal,temporal cortex,etc.The brain regions with relative hypometabolism were bilateral asymmetric lentiform_nucleus,part of temporal,occipital cortex,etc.2 Analysis results of brain network topological attributes based on graph theory2.1 Hub nodes:The brain regions and locations of the hub nodes in brain networks were inconsistent among early,moderate PD groups and normal control group.The hub nodes of brain network in normal control group were temporal_mid₁,frontal_sup_orb₁,temporal_inf₁,etc.The hub nodes of brain network in early PD group were hippocampus₁,parahippocampal₁,frontal_inf_oper₁,etc.The hub nodes of brain network in moderate PD group were temporal_inf₁,frontal_inf_oper₁,temporal_sup₁,etc.2.2 Global attributes of brain networks:Compared with normal control group,the small-world attributes and assortativities of brain networks decreased,and the global efficiencies of brain networks increased,in early and moderate PD groups.3 Seed analysis results of brain networks based on glucose metabolism3.1 Compared with normal control group,relatively abnormal brain network connections in early PD group:The internal brain networks of corpus striatum（dopamine nerve lesion regions）and thalamus,and their brain network connections with some limbic system brain regions,occipital,temporal,frontal gyri,olfactory cortex,etc were relatively weakened.3.2 Compared with normal control group,relatively abnormal brain network connections in moderate PD group:The selected seed points had more brain regions with relatively weakened brain network connectivity than those with relatively enhanced brain network connectivity,especially putamen,thalamus,temporal_mid,etc.3.3 Compared with early PD group,relatively abnormal brain network connections in moderate PD group:Seed points with more relatively enhanced connective brain regions were cingulum_mid,paracentral_lobule,and putamen_r,etc.Seed points with more relatively weakened connective brain regions were thalamus,insula,temporal_mid,etc.Conclusions1 Comparative analysis of glucose metabolism images in early and moderate PD groups with 18F-FDG PET/CTThere were characteristic brain regions with relatively abnormal 18F-FDG metabolism in early and moderate PD groups.Compared with early PD group,claustrum,midbrain,supp_motor_area₁,etc were new emerging brain regions with relatively abnormal metabolism,meanwhile the areas of relative hypermetabolism in the pons,cerebellum and relative hypometabolism in the parietal,occipital lobes were larger in moderate PD group.2 Result analysis of brain network topological attributes2.1 The comprehensive orderings of some hub nodes in the temporal and occipital lobes were weakened,while the comprehensive orderings of some hub nodes in the limbic system and the frontal lobe were enhanced in early and moderate PD groups.Compared with early PD group,the comprehensive orderings of some hub nodes in the limbic system were weakened,while the comprehensive orderings of some hub nodes in the frontal and occipital lobe were enhanced in moderate PD group.2.2 The small-world attributes and assortativities of brain networks decreased,and the global efficiencies increased,in early and moderate PD groups.3 Comprehensive analysis of the abnormal glucose metabolism images,the hub nodes in brain networks,and the brain network connections of seed points with 18F-FDG PET/CT in early and moderate PD groups3.1 The selected seed points had more brain regions with relatively weakened brain network connectivity than those with relatively enhanced brain network connectivity in moderate PD.Some seed points of occipital gyrus showed relatively enhanced bilateral asymmetric brain network connections dominantly in early PD group,while showed relatively weakened bilateral asymmetric brain network connections dominantly in moderate PD group.3.2 The seed points with more brain network connections to the hub nodes in early PD group were more connected in a relatively weakened way,while the seed points with more brain network connections to the hub nodes in moderate PD group were more connected in a relatively enhanced way.There were more brain regions with relatively enhanced brain network connectivity among brain regions with relatively abnormal 18F-FDG metabolism in early and moderate PD groups.