Putamen Research Articles

Iron Content in Deep Gray Matter as a Function of Age Using Quantitative Susceptibility Mapping: A Multicenter Study.

PurposeTo evaluate the effect of resolution on iron content using quantitative susceptibility mapping (QSM); to verify the consistency of QSM across field strengths and manufacturers in evaluating the iron content of deep gray matter (DGM) of the human brain using subjects from multiple sites; and to establish a susceptibility baseline as a function of age for each DGM structure using both a global and regional iron analysis.MethodsData from 623 healthy adults, ranging from 20 to 90 years old, were collected across 3 sites using gradient echo imaging on one 1.5 Tesla and two 3.0 Tesla MR scanners. Eight subcortical gray matter nuclei were semi-automatically segmented using a full-width half maximum threshold-based analysis of the QSM data. Mean susceptibility, volume and total iron content with age correlations were evaluated for each measured structure for both the whole-region and RII (high iron content regions) analysis. For the purpose of studying the effect of resolution on QSM, a digitized model of the brain was applied.ResultsThe mean susceptibilities of the caudate nucleus (CN), globus pallidus (GP) and putamen (PUT) were not significantly affected by changing the slice thickness from 0.5 to 3 mm. But for small structures, the susceptibility was reduced by 10% for 2 mm thick slices. For global analysis, the mean susceptibility correlated positively with age for the CN, PUT, red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). There was a negative correlation with age in the thalamus (THA). The volumes of most nuclei were negatively correlated with age. Apart from the GP, THA, and pulvinar thalamus (PT), all the other structures showed an increasing total iron content despite the reductions in volume with age. For the RII regional high iron content analysis, mean susceptibility in most of the structures was moderately to strongly correlated with age. Similar to the global analysis, apart from the GP, THA, and PT, all structures showed an increasing total iron content.ConclusionA reasonable estimate for age-related iron behavior can be obtained from a large cross site, cross manufacturer set of data when high enough resolutions are used. These estimates can be used for correcting for age related iron changes when studying diseases like Parkinson’s disease, Alzheimer’s disease, and other iron related neurodegenerative diseases.

Brain functional connectivity in individuals with psychogenic nonepileptic seizures (PNES): An application of graph theory

ObjectiveTo determine brain functional connectivity (FC), based on the graph theory, in individuals with psychogenic nonepileptic seizures (PNES), in order to better understand the mechanisms underlying this disease. MethodsTwenty-three patients with PNES and twenty-five healthy control subjects were examined. Alterations in FC within the whole brain were examined using resting-state functional magnetic resonance imaging (MRI). We calculated measures of the nodal degree, a major feature of the graph theory, for all the cortical and subcortical regions in the brain. Pearson correlation was performed to determine the relationship between nodal degree in abnormal brain regions and patient characteristics. ResultsThe nodal degrees in the right caudate (CAU), left orbital part of the left inferior frontal gyrus (ORBinf), and right paracentral lobule (PCL) were significantly greater (i.e. hyper-connectivity) in individuals with PNES than in healthy control subjects. On the other hand, a lesser nodal degree (i.e. hypo-connectivity) was detected in several other brain regions including the left and right insula (INS), as well as the right putamen (PUT), and right middle occipital gyrus (MOG). ConclusionOur findings suggest that the FC of several major brain regions can be altered in individuals with PNES. Areas with hypo-connectivity may be involved in emotion processing (e.g., INS) and movement regulation (e.g., PUT), whereas areas with hyper-connectivity may play a role in the inhibition of unwanted movements and cognitive processes (e.g., CAU).

MRI-Based Radiomics of Basal Nuclei in Differentiating Idiopathic Parkinson's Disease From Parkinsonian Variants of Multiple System Atrophy: A Susceptibility-Weighted Imaging Study.

ObjectivesTo investigate the value of MRI-based radiomic model based on the radiomic features of different basal nuclei in differentiating idiopathic Parkinson’s disease (IPD) from Parkinsonian variants of multiple system atrophy (MSA-P).MethodsRadiomics was applied to the 3T susceptibility- weighted imaging (SWI) from 102 MSA-P patients and 83 IPD patients (allocated to a training and a testing cohort, 7:3 ratio). The substantia nigra (SN), caudate nucleus (CN), putamen (PUT), globus pallidus (GP), red nucleus (RN), and subthalamic nucleus (STN) were manually segmented, and 396 features were extracted. After feature selection, support vector machine (SVM) was generated, and its predictive performance was calculated in both the training and testing cohorts using the area under receiver operating characteristic curve (AUC).ResultsSeven radiomic features were selected from the PUT, by which the SVM classifier achieved the best diagnostic performance with an AUC of 0.867 in the training cohort and an AUC of 0.862 in the testing cohort. Furthermore, the combined model, which incorporating part III of the Parkinson’s Disease Rating Scale (UPDRSIII) scores into radiomic features of the PUT, further improved the diagnostic performance. However, radiomic features extracted from RN, SN, GP, CN, and STN had moderate to poor diagnostic performance, with AUC values that ranged from 0.610 to 0.788 in the training cohort and 0.583 to 0.766 in the testing cohort.ConclusionRadiomic features derived from the PUT had optimal value in differentiating IPD from MSA-P. A combined radiomic model, which contained radiomic features of the PUT and UPDRSIII scores, further improved performance and may represent a promising tool for distinguishing between IPD and MSA-P.

Histogram Analysis of Quantitative Susceptibility Mapping for the Diagnosis of Parkinson's Disease

To investigate the diagnostic performance of histogram analysis combined with quantitative susceptibility mapping (QSM) for differentiating Parkinson's disease (PD) patients from healthy controls. We included 35 patients with PD diagnosed by two neurologists from August 2019 to January 2020 in our hospital in this prospective study. The clinical diagnosis was based on the Movement Disorder Society Clinical Diagnostic Criteria for PD. At the same time, 23 healthy volunteers matched for age and sex were recruited as controls. The Mini Mental State Examination, the third part of the Parkinson's Disease Rating Scale, the Hoehn & Yahr stages, and disease duration (year) were used to assess the PD patients. QSM was performed using a 3T MR scanner. The regions of interest were depicted according to the head of the caudate nucleus(CN), globus pallidus(GP), putamina (PUT), thalmus(TH), substantia nigra (SN), red nucleus(RN), and dentate nucleus. Then the corresponding histogram features were extracted. The Mann-Whitney U test was used to identify significant histogram features for differentiating PD patients from healthy controls. Area under the receiver operating characteristics curve (AUC) analysis was conducted to evaluate the diagnostic performance of all significant histogram features. Multivariate logistic regression analysis was performed to identify the best combined model for all seven nuclei. Differences among the AUCs were compared pairwise. Histogram features in all nuclei except TH showed significant differences between the groups. Among the single features, the 10th percentile of SN (SNP10) yielded the highest AUC of 0.894, with the highest specificity of 86.86% for differentiating PD patients from healthy controls. The 75th percentile of PUT (PUTP75) yielded the highest sensitivity of 97.14%. In the multivariate logistic regression analysis, SNP10 combined with PUTP75 yielded the highest diagnostic performance with the highest AUC of 0.911, the highest specificity of 91.30% and an excellent sensitivity of 92.40%. QSM combined with histogram analysis successfully distinguished PD patients from healthy controls, and the result was notably superior to the mean value.

Iron deposition and atrophy in cerebral grey matter and their possible association with serum iron in relapsing-remitting multiple sclerosis

PurposeThe present study was carried out to investigate any possible linkage between cerebral grey matter volumetric, iron changes, white matter's lesions load and serum iron levels in a group of relapsing-remitting multiple sclerosis (RRMS) patients. Materials and methodsSixty-five RRMS patients along with thirty-four age-matched healthy controls (HCs) were recruited. Serum samples were isolated from blood samples which were collected in vacutainer plain tubes individually from both groups. Both groups were scanned at 1.5 T magnetic resonance imaging (MRI) using the following 3D sequences; T1-weighted gradient echo (MPRAGE), T2*-weighted gradient echo and T2-weighted fluid-attenuated inversion recovery (FLAIR). ResultsSignificant differences were observed between the RRMS patients and HCs for cortical and deep grey matter (dGM) volumes where cortical and dGM volumes in RRMS patient were significantly smaller than those in HCs. While iron deposition in the cortex, putamen (PT) and globus pallidus (GP) of RRMS patients were significantly higher than those of HCs, iron levels in thalamus (TH) and serum were significantly lower in RRMS compared to those in HCs. Except for T2 lesion load, none of volumetric measures showed any association with patients' disability status. Cerebral grey matter's iron changes did not show any association with those of serum. ConclusionSmaller cortical and subcortical grey matter volumes in RRMS patients compared to HCs were detected. None of the volumetric measures showed any association with patients' disability status. RRMS patients showed increased iron levels in the PT, GP and cortex and decreased levels in the TH and serum.

The Effect of Iron Accumulation in the Basal Ganglia on the Dysfunction of the Extrapyramidal System in Parkinson’s Disease

Parkinson’s disease (PD) is a chronic, steadily progressing disease of the central nervous system (CNS) that belongs to the group of synucleinopathies, which causes significant damage to the health of the elderly and leads to disability in the process of progression. Diffusion-tensor MRI and the susceptibility-weighted imaging (SWI) protocol are modern non-invasive neuroimaging techniques that, when used together with patients with PD, can not only assess the distribution and pathological deposition of iron in the basal ganglia, but also its likely effect on the dysfunction of extrapyramidal system structures. Goal. To determine the quantitative content of iron in the basal ganglia in patients with stage II and III (H/Y) Parkinson ’s disease and evaluate its effect on the dysfunction of the components of the extrapyramidal system. Material and methods . We examined 67patients with PD with II (n = 32) andIII (n = 35) Hoehn/Yahr (H/Y) stages. To everyone was performed a brain scan on a Siemens TrioTim high-field MRI scanner (3T) using the pulse sequence SWI and diffusion-tensor MRI. A quantitative assessment of the degree of iron deposition was carried out using SPIN software in regions of interest (ROIs) on both sides: the dentate nucleus (DN), the substantia nigra (SN), the red nucleus (RN), the putamen (PUT), the globus pallidusm (GP), the head of the caudate nucleus (CN). Also, in the projection of ROIs, the fractional anisotropy (FA) values was calculated. Results. Significant (p <0,05) lower FA values were found in left GP and right RN in patients with stage III (H/Y) in comparison with patients with stage II (H/Y). In patients with stage II (H/Y), significant positive correlations were found between the FA values in the left PUT and the hypointensity of SN, GP, RN (all on both sides) and right CN. The FA value in the right PUT correlated with hypointensity of the left SN. The FA value in the left RN had correlations with the hypointensity of the SN, GP (all on both sides), the right RN, the left PUT, and the right CN. In patients with stage III (H/Y), the only reliable positive correlations were found between the FA values and the hypointensity of the ROIs: left CN and left PUT, right PUT and left CN, left SN and right CN, respectively. SWI hypointensity of the left RN, the right PUT, the left CN, and the right GP correlated positively with the FA value in the right SN. The decrease FA value in the left internal GP correlated with the hypointensity of the right DN and right RN. Conclusion. The deposition of iron in the basal ganglia in PD makes a significant contribution to the progression of the disease and affects the formation of most motor manifestations in this category of patients. A dynamic non-invasive assessment of the degree of iron accumulation in the components of the extrapyramidal system will more closely monitor the course of the neurodegenerative process and form observation groups for the risk of PD complications.

Parkinson's Disease Diagnosis Using Neostriatum Radiomic Features Based on T2-Weighted Magnetic Resonance Imaging.

Background: Parkinson's disease (PD) is a neurodegenerative disease in which the neostriatum, including the caudate nucleus (CN) and putamen (PU), has an important role in the pathophysiology. However, conventional magnetic resonance imaging (MRI) lacks sufficient specificity to diagnose PD. Therefore, the study's aim was to investigate the feasibility of using a radiomics approach to distinguish PD patients from healthy controls on T2-weighted images of the neostriatum and provide a basis for the clinical diagnosis of PD.Methods: T2-weighted images from 69 PD patients and 69 age- and sex-matched healthy controls were obtained on the same 3.0T MRI scanner. Regions of interest (ROIs) were manually placed at the CN and PU on the slices showing the largest respective sizes of the CN and PU. We extracted 274 texture features from each ROI and then used the least absolute shrinkage and selection operator regression to perform feature selection and radiomics signature building to identify the CN and PU radiomics signatures consisting of optimal features. We used a receiver operating characteristic curve analysis to assess the diagnostic performance of two radiomics signatures in a training group and estimate the generalization performance in the test group.Results: There were no significant differences in the demographic and clinical characteristics between the PD patients and healthy controls. The CN and PU radiomics signatures were built using 12 and 7 optimal features, respectively. The performance of the two radiomics signatures to distinguish PD patients from healthy controls was good. In the training and test groups, the AUCs of the CN radiomics signatures were 0.9410 (95% confidence interval [CI]: 0.8986–0.9833) and 0.7732 (95% CI: 0.6292–0.9173), respectively, and the AUCs of the PU radiomics signature were 0.8767 (95% CI: 0.8066–0.9469) and 0.7143 (95% CI: 0.5540–0.8746), respectively. Vertl_GlevNonU_R appeared simultaneously in both the CN and PU radiomics signatures as an optimal feature. A t-test analysis revealed significantly higher levels of texture values of the CN and PU in the PD patients than healthy controls (P < 0.05).Conclusion: Neostriatum radiomics signatures achieved good diagnostic performance for PD and potentially could serve as a basis for the clinical diagnosis of PD.

Clinical characteristics and prognostic factors of insular glioblastomas

Objective To explore the clinical characteristics and prognostic factors of insular glioblastomas. Methods Clinical data of 44 patients with insular glioblastomas in Chinese Glioma Genome Atlas(CGGA) databases from July 2006 to June 2013 were evaluated. All patients underwent tumor resection. Among them, 27 underwent adjuvant radiochemotherapy and 17 underwent no postoperative adjuvant therapy. Progression-free survival (PFS) and overall survival (OS) of all patients were analyzed by Kaplan-Meier method. Furthermore, multivariate Cox regression analysis was used to investigate the prognostic clinical factors. Results In a total of 44 patients, 33 (75.0%) had a history of epileptic seizure, 11 (25.0%) had isocitrate dehydrogenase 1 (IDH1) mutation, 19 (43.2%) had O6-methy-lguanine-DNA-methyltransferase (MGMT) methylation, and 42 (95.5%) had tumor enhancement.Based on Yasargil′s classification, there were type 3A in 2 cases, type 3B in 27 cases and type 5A/B in 15 cases. Based on Saito′s classification, there were 2 cases confined to the insular cortex, 9 cases with invasion to the frontal lobe via the anterior circumferential sulcus, 16 cases with invasion to the temporal lobe via the lower circumferential sulcus, and 17 cases with invasion to multiple directions via more than 2 circumferential sulci. Based on Moshe′s classification, there were 35 cases with envelopment or invasion of the lenticulostriate artery, while no invasion was reported in the remaining 9 cases. Based on the putamen classification, there were 38 cases with various degrees of putamen invasion, and the remaining 6 cases had no involvement of the putamen. Kaplan-Meier curve showed that the median PFS of all patients was 278 d and the median OS was 435 d. Multivariate Cox regression analysis showed that tumor volume < median (HR = 0.390, 95% CI: 0.189-0.802, P=0.011), IDH1 mutation (HR=0.391, 95% CI: 0.175-0.876, P=0.023) and postoperative radiochemotherapy (HR=0.346, 95% CI: 0.162-0.738, P=0.006) were independent protective factors for PFS. However, MGMT methylation (HR=0.371, 95% CI: 0.181-0.758, P=0.007), tumor resection degree ≥90% (HR=0.412, 95% CI: 0.194-0.875, P=0.021) and postoperative radiochemotherapy (HR=0.347, 95% CI: 0.170-0.708, P=0.004) were independent protective factors for OS. Conclusions Clinical characteristics of insula glioblastomas include relatively lower incidence, stronger invasiveness, lower total resection ratio and poorer prognosis. Maximum resection and standard postoperative radiochemotherapy may lead to a better outcome. Key words: Glioblastoma; Insula; Prognosis; Multivariate analysis

Different iron deposition patterns in hemodialysis patients with and without restless legs syndrome: a quantitative susceptibility mapping study

ObjectiveBrain iron deposition in hemodialysis (HD) patients increases over time. Iron deficiency in gray matter nuclei has been reported to lead to idiopathic restless legs syndrome (RLS) symptoms. Regardless of unpleasant RLS sensations, the patterns of iron deposition between hemodialysis patients with RLS (HD-RLS) and hemodialysis patients without RLS (HD-nRLS) are still unclear. To evaluate the differences in iron deposition patterns between HD-RLS and HD-nRLS patients, we utilized quantitative susceptibility mapping (QSM). MethodsIn sum, 24 HD-RLS patients, 25 HD-nRLS patients and 30 age- and sex-matched healthy controls (HCs) were enrolled. The QSM was used to assess susceptibility values of the regions of interest (ROIs), including the caudate nucleus (CN), putamen (PUT), globus pallidus (GP), thalamus (THA), substantia nigra (SN), red nucleus (RN) and dentate nucleus (DN). ResultsHD duration was significantly longer in HD-RLS patients than in HD-nRLS patients (P < 0.05). The susceptibility of HD-RLS and HD-nRLS patients in PUT was higher than that in HCs (P < 0.05), illustrating elevated iron content in the nucleus. Compared with HD-nRLS patients, HD-RLS patients demonstrated reduced susceptibility in CN and PUT (both P < 0.05). Compared with HCs, HD-RLS patients displayed decreased susceptibility in DN (P < 0.05). ConclusionsDifferent iron deposition patterns between HD-RLS and HD-nRLS patients in PUT and DN, which further support disturbed sensory processing in RLS, may be involved in RLS pathogenesis in HD patients.

Distinct gradients of various neurotransmitter markers in caudate nucleus and putamen of the human brain.

The caudate nucleus (CN) and the putamen (PUT) as parts of the human striatum are distinguished by a marked heterogeneity in functional, anatomical, and neurochemical patterns. Our study aimed to document in detail the regional diversity in the distribution of dopamine (DA), serotonin, γ‐aminobuturic acid, and choline acetyltransferase within the CN and PUT. For this purpose we dissected the CN as well as the PUT of 12 post‐mortem brains of human subjects with no evidence of neurological and psychiatric disorders (38–81 years old) into about 80 tissue parts. We then investigated rostro‐caudal, dorso‐ventral, and medio‐lateral gradients of these neurotransmitter markers. All parameters revealed higher levels, turnover rates, or activities in the PUT than in the CN. Within the PUT, DA levels increased continuously from rostral to caudal. In contrast, the lowest molar ratio of homovanillic acid to DA, a marker of DA turnover, coincided with highest DA levels in the caudal PUT, the part of the striatum with the highest loss of DA in Parkinson’s disease (N. Engl. J. Med., 318, 1988, 876). Highest DA concentrations were found in the most central areas both in the PUT and CN. We observed an age‐dependent loss of DA in the PUT and CN that did not correspond to the loss described for Parkinson’s disease indicating different mechanisms inducing the deficit of DA. Our data demonstrate a marked heterogeneity in the anatomical distribution of neurotransmitter markers in the human dorsal striatum indicating anatomical and functional diversity within this brain structure.

Quantification and discriminative power of 18F-FE-PE2I PET in patients with Parkinson's disease.

Dopamine transporter (DAT) imaging is an important adjunct in the diagnostic workup of patients with Parkinsonism. 18F-FE-PE2I is a suitable PET radioligand for DAT quantification and imaging with good pharmacokinetics. The aim of this study was to determine a clinical optimal simplified reference tissue-based image acquisition protocol and to compare the discriminatory value and effect size for 18F-FE-PE2I to that for 123I-FP-CIT scan currently used in clinical practice. Nine patients with early Parkinson's disease (PD, 64.3 ± 6.8 years, 3M), who had previously undergone a 123I-FP-CIT scan as part of their diagnostic workup, and 34 healthy volunteers (HV, 47.7 ± 16.8 years, 13M) underwent a 60-min dynamic 18F-FE-PE2I PET-MR scan on a GE Signa 3T PET-MR. Based on dynamic data and MR-based VOI delineation, BPND, semi-quantitative uptake ratio and SUVR[t1-t2] images were calculated using either occipital cortex or cerebellum as reference region. For start-and-end time of the SUVR interval, three time frames [t1-t2] were investigated: [15-40] min, [40-60] min, and [50-60] min postinjection. Data for putamen (PUT) and caudate nucleus-putamen ratio (CPR) were compared in terms of quantification bias versus BPND and discriminative power. Using occipital cortex as reference region resulted in smaller bias of SUVR with respect to BPND + 1 and higher correlation between SUVR and BPND + 1 compared with using cerebellum, irrespective of SUVR [t1-t2] interval. Smallest bias was observed with the [15-40]-min time window, in accordance with previous literature. The correlation between BPND + 1 and SUVR was slightly better for the late time windows. Discriminant analysis between PD and HV using both PUT and CPR SUVRs showed an accuracy of ≥ 90%, for both reference regions and all studied time windows. Semi-quantitative 123I-FP-CIT and 18F-FE-PE2I values and relative decrease in the striatum for patients were highly correlated, with a higher effect size for 18F-FE-PE2I for PUT and CPR SUVR. 18F-FE-PE2I is a suitable radioligand for in vivo DAT imaging with high discriminative power between early PD and healthy controls. Whereas a [15-40]-min window has lowest bias with respect to BPND, a [50-60]-min time window at pseudoequilibrium can be advocated in terms of clinical feasibility with optimal discriminative power. The occipital cortex may be slightly preferable as reference region because of the higher time stability, stronger correlation of SUVR with BPND + 1, and lower bias. Moreover, the data suggest that the diagnostic accuracy of a 10-min static 18F-FE-PE2I scan is non-inferior compared with 123I-FP-CIT scan used in standard clinical practice.

The role of iron in Parkinson's disease monkeys assessed by susceptibility weighted imaging and inductively coupled plasma mass spectrometry

Mounting evidences indicated that elevated iron levels in the substantia nigra (SN) have been concerned as the underlying mechanisms of neurodegenerative diseases, including Parkinson's disease (PD). The present study used the 1-Methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine (MPTP)-treated cynomolgus monkeys for PD to evaluate the usability of SWI for assessing iron deposition in the cerebral nuclei of PD. The results showed that susceptibility-weighted imaging (SWI) phase values of the ipsilateral (MPTP-lesion side) SN of MPTP-treated monkeys were lower than those in the contralateral SN of MPTP-treated monkeys and the same side of Control monkeys, suggesting that iron deposition were elevated in the affected side SN of MPTP-treated monkeys. Whereas MPTP has not effects on the SWI phase values in other detected brain regions of monkeys, including red nucleus (RN), putamen (PUT) and caudate nucleus (CA). Furthermore, ICP-MS results showed that MPTP increased the iron levels in MPTP injection side, but no in the ipsilateral striatum. Additionally, MPTP treatment did not affect the calcium and manganese levels in the detected brain regions of monkeys. However, Pearson correlation analysis results indicated that there were not relationship between SWI phase values in MPTP-lesion side of SN with the behavioral score, tyrosine hydroxylase (TH)-positive cells number and iron levels in the MPTP-lesion side of midbrain. Taken together, the results confirm the involvement of SN iron accumulations in the MPTP-treated monkey models for PD, and indirectly verify the usability of SWI for the measurement of iron deposition in the cerebral nuclei of PD.

Diffusion kurtosis imaging characteristics of brain gray matter nucleus microstructure in Parkinson's disease with different movement disorder subtypes

Objective To investigate the difference in the microstructure of gray matter nucleus in different movement subtypes of Parkinson’s disease (PD) by diffusion kurtosis imaging (DKI) technique, and to analyze the correlation with clinical manifestations. Methods Ninety-seven patients with PD and 83 healthy controls performed conventional MRI sequence and DKI sequence scan. The PD patients were classified into gait disorder subtype (PIGD, n=57) and tremor dominant subtype (TD, n=40)subtypes according to motor symptoms. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), radial diffusivity(Dr), mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Dr) maps and data were generated by software after processing. DKI was performed for all subjects and data was collected from different brain regions in both hemispheres, including red nucleus(RN), substantia nigra pars reticulate(SNr), substantia nigra pars compacta(SNc), putamen(PUT), globus pallidus(GP), head of caudate nucleus (CN)and thalamus(THA). Results TD showed a higher MMSE score(P=0.019), but lower modified Hoehn-Yahr score than that in PIGD (P 0.05). Moreover, there was no significant correlation between DKI value and disease duration, MMSE score or Hoehn-Yahr scale (P>0.05) in TD and PIGD. Conclusion There is heterogeneity of clinical symptoms between these two subgroups of PD. DKI can quantify the microstructural changes of grey matter nucleus in different type PD patient. Key words: Parkinson's disease; Movement disorder subtypes; Diffusion kurtosis imaging; Heterogeneity

Magnetic Susceptibility in Normal Brains of Young Adults Based on Quantitative Susceptibility Mapping.

To explore the changes of brain susceptibility of different sides and genders in healthy young adults using quantitative susceptibility mapping (QSM). Totally 42 healthy young right-handed adults underwent conventional brain magnetic resonance imaging and QSM scans, and the susceptibility maps were obtained by image post-processing software. Then the regions-of-interest (ROI) of bilateral frontal gray matter (FGM), frontal white matter (FWM), caudate (CA), globus pallidus (GP), putamen (PU), thalamus (TH), substantia nigra (SN), red nucleus (RN), dentate nucleus (DN), pons (PO), and corpus callosum (CC) were manually drawn to obtain magnetic susceptibility on the susceptibility maps. The magnetic susceptibility of each ROI was compared between 2 sides and genders by Wilcoxon rank sum test. Magnetic susceptibility of bilateral ROI was the highest in GP, followed by SN, and the lowest in FWM. No statistically significant difference was found in susceptibility of bilateral FGM, FWM, CA, GP, PU, TH, SN, RN, DN, PO, or CC. Magnetic susceptibility in CA significantly different genders. Brain magnetic susceptibility measured by QSM can be used to quantitatively assess brain iron concentrations.

Changes of dopamine D2 receptor in patients with insomnia and its clinical significance

Objective To explore the changes of dopamine D2 receptor in dopamine pathway in insomnia patients and discuss its clinical significance. Methods From January 2016 to December 2016, 15 patients with insomnia (1 male, 14 females, age: (44.3±8.6) years) and 15 gender-/age- matched-healthy volunteers (control group; 3 males, 12 females, age: (40.5±9.0) years) were included to undergo resting brain 11C-Raclopride PET/CT imaging. The D2 receptor binding potential (BPND) of the dopamine pathway was calculated by molecular imaging and kinetic analysis toolbox (MIAKAT) software. The BPND, Hamilton depression scale (HAMD), transient and graphics memory scale results were compared with two-sample t test and Mann-Whitney u test between the two groups. Pearson correlation analysis was used to evaluate the correlation between BPND (nucleus accumbens, caudate nucleus, putamen) and Pittsburgh sleep quality index (PSQI), HAMD, course of disease, transient memory and graphical memory scale scores in the patient group. Results The BPND in bilateral putamen, nucleus accumbens and left caudate nucleus of patients was lower than that of controls(left putamen: z=-2.717, right putamen: z=-2.883, both P 0.05). The scores of HAMD in the patient group were higher than those in control group (t=10.273, P<0.01), while the scores of instantaneous memory (t=-4.888, P<0.01) and graphical memory scale (t=-2.624, P<0.05) were lower. There were significant negative correlations between the BPND of bilateral nucleus accumbens, caudate nucleus and putamen and the course of insomnia in the patient group (r range: -0.761 to -0.682, all P<0.01). Conclusion Patients with insomnia have abnormal neurotransmitter system of dopamine D2 and it may play a role in the pathogenesis of insomnia. Key words: Sleep initiation and maintenance disorders; Receptors, dopamine; Raclopride; Carbon radioisotopes; Positron-emission tomography; Tomography, X-ray computed; Magnetic resonance imaging

Metabolic patterns of 11C-CFT and 18F-FDG PET/CT imaging in tremor and non-tremor Parkinson′s disease

Objective To investigate the metabolic patterns of 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and 18F-fluorodeoxyglucose (FDG) PET/CT imaging in patients with tremor and non-tremor Parkinson′s disease (PD). Methods From March 2018 to March 2019, 28 PD patients (19 tremor patients: 14 males and 5 females, age: (59.9±11.4) years; 9 non-tremor patients: 3 males and 6 females, age: (62.6±9.0) years) were enrolled. For the two groups, the 11C-CFT uptake values in caudate nucleus, anterior putamen and posterior putamen as well as 18F-FDG uptake values in all brain regions were calculated by regions of interest (ROI) method. Two-sample t test or Mann-Whitney u test were used to analyze the data. Results Caudate nucleus 11C-CFT uptake in PD patients with tremor was higher than that without tremor (3.03±0.51 vs 2.60±0.62; t=2.687, P<0.05). Yet thalamus glucose uptake of non-tremor PD patients showed more active than tremor patients (1.14±0.05 vs 1.10±0.03; t=3.449, P<0.01). Sorted by modified Hoehn-Yahr stage, tremor patients in advanced stage (stage≥2.5) were characterized by glucose uptake increase in the putamen and cerebellum compared with non-tremor advanced group (1.27±0.04 vs 1.21±0.05, 0.94±0.04 vs 0.86±0.08; t values: 2.695 and 2.492, both P<0.05). Metabolic decrease in the premotor areas was observed in tremor patients in advanced stage compared with early stage (1.07±0.02 vs 1.10±0.03; t=2.053, P<0.05). Conclusion 11C-CFT and 18F-FDG PET/CT imaging can indicate different metabolic patterns between tremor and non-tremor PD, thus providing information for clinical practice and differential diagnosis. Key words: Parkinson disease; Tremor; Positron-emission tomography; Tomography, X-ray computed; Tropanes; Deoxyglucose

Correlations between striatal dopamine transporter distribution, glucose metabolism and clinical symptoms in Parkinson′s disease

Objective To investigate the correlations among striatal dopamine transporter (DAT) distribution, glucose metabolism and Parkinson′s disease (PD) clinical symptoms. Methods Twenty-five clinically confirmed idiopathic PD patients (17 males, 8 females, age: (59.8±9.2) years) who underwent 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and 18F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed. The detailed clinical scores were systematically collected from all patients. Correlations between DAT distribution, glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis. Results There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores, non-motor symptoms scale (NMSS) scores, activity of daily living scale (ADL) scores (r values: 0.580, 0.522, 0.557, all P 0.05). The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values: -0.502, -0.522, both P 0.05). The presence of the significant correlations between UPDRS motor scores, ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values: from -0.90 to -0.47, all P<0.05). The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms. The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values: 0.47-0.90, both P<0.01), precentral gyrus and insula (r values: -0.90 to -0.47, all P<0.01). Conclusion The correlations between DAT distribution, glucose metabolism and PD clinical symptoms are complicated, which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms. Key words: Parkinson disease; Dopamine plasma membrane transport proteins; Signs and symptoms; Positron-emission computed; Deoxyglucose

Correlation and differential diagnostic value of 18F-FDG imaging and arterial spin labeling cerebral perfusion imaging acquired by synchronous PET/MR in Parkinsonism

Objective To discuss the correlation between 18F-fluorodeoxyglucose (FDG) imaging and arterial spin labeling perfusion weighted imaging (ASL-PWI) using synchronous PET/MR, and explore the feasibility of 18F-FDG PET and ASL for differential diagnosis in Parkinsonism (PS). Methods A retrospective analysis was performed in 24 patients with Parkinson′s disease (PD), 10 patients with multiple system atrophy (MSA) and 6 patients with progressive supranuclear palsy (PSP) who all underwent 18F-FDG PET/MR imaging from October 2017 to December 2018 (15 males, 25 females, age: 34-77 years). Synchronously acquired data, including MRI T1, 18F-FDG PET and three dimensional (3D) ASL-PWI were extracted. T1 structure image was used to register with standard brain template, and the personalized brain template of each patient was obtained. Then, the templates were matched to the corresponding PET and ASL-PWI images, and the mean standardized uptake value (SUVmean) and mean cerebral blood flow (CBFmean) of each brain region could be extracted. Pearson correlation analysis was used to evaluate the correlation between SUVmean and CBFmean of the whole brain and the regions of interest (ROI; caudate nucleus, putamen, midbrain, pons and cerebellum). One-way analysis of variance and least significant difference t test were used to evaluate the characteristics of SUVmean and CBFmean in different diagnostic groups. The diagnostic values of SUVmean and CBFmean in different ROI were evaluated with receiver operating characteristic (ROC) curve analysis. Results A total of 2 800 pairs of SUVmean and CBFmean were obtained from 40 cases in 3 groups. The overall correlation between them was good (r=0.468, P<0.01). There were also significant correlations between SUVmean and CBFmean in caudate nucleus, putamen, pons and cerebellum (r values: 0.346-0.492, all P<0.05). The CBFmean of cerebellum in MSA group was significantly lower than that in PD group ((36.92±11.35) vs (47.92±10.75) ml·100 g-1·min-1;F=4.817, t=2.675, P<0.05). Compared to the PSP group, CBFmean in caudate nucleus was higher in PD group ((30.02±3.51) vs (40.21±8.13) ml·100 g-1·min-1;F=5.393, t=2.969, P<0.05). The similar results were obtained for SUVmean. To differentiate PD with MSA, CBFmean of cerebellum possessed the highest diagnostic efficiency, with the area under ROC curve (AUC), sensitivity and specificity reaching 0.792, 83.3% and 70.0% respectively. To differentiate PSP with PD or MSA, CBFmean in caudate nucleus had the highest diagnostic efficiency, and the AUC were 0.903 and 0.933 respectively. Conclusions In patients with PD, MSA and PSP, the level of 18F-FDG glucose metabolism is in good agreement with the ASL cerebral blood flow perfusion obtained by synchronous PET/MR. The distribution characteristics of specific ROI in both PET and MR imaging can be helpful to the differential diagnosis of PS. Key words: Parkinsonian disorders; Positron-emission tomography; Magnetic resonance imaging; Diagnosis, differential; Deoxyglucose

Altered topological properties in white matter structural networks in patients with schizophrenia

Objective To explore the changes of whole brain white matter (WM) structural network topological property in patients with schizophrenia (SP) and the associations between WM networks topological efficiency and clinical variables in patients. Methods Deterministic tractography was used to construct the WM networks of 59 patients with SP (patients group) and 41 age-, handedness-, and gender-matched healthy controls (HCs), and graph theoretical methods were applied to investigate abnormalities in the global and nodal properties of the WM network in these patients.Partial correlation analysis was used to analyze the relationship between global and nodal properties of the WM network and clinical variables in patients with SP. Results Both the patients with SP and HCs showed small-world organization of the WM networks.However, compared with HCs, the patients with SP exhibited significant abnormal global topology, including increased shortest path length (t=7.95, P=0.0001) and decreased global efficiency (30.83±16.08, 8.25±6.13, t=-9.81, P=0.002), clustering coefficiency (0.03±0.01, 0.02±0.01, t=-4.48, P=0.0003), the average clustering coefficiency (t=-8.28, P=0.002), the small-worldness (3.92±0.79, 2.79±0.56, t=-7.82, P=0.001) of their WM structural networks(all P<0.005, FDR corrected). Further, the patients with SP showed a reduction in nodal efficiency predominately in the cingulate gyrus (t=-4.11, P=0.000), superior occipital gyrus (t=-6.05, P=0.002), superior temporal gyrus (t=-10.46, P=0.001), middle temporal gyrus (t=-10.38, P=0.000), thalamus (t=-6.10, P=0.000) and putamen (t=-8.38, P=0.000) (P<0.005, FDR corrected). Partial correlation results showed that there was no significant correlation between global topological properties, node efficiency and clinical symptoms in patients group(Eglob: r=-0.14, P=0.279; Eloc: r=-0.06, P=0.628; Lp: r=0.28, P=0.031; Cp: r=0.27, P=0.043; λ: r=-0.18, P=0.166; γ: r=-0.29, P=0.026; σ: r=0.26, P=0.048; nEglob: r=0.36, P=0.005; nEloc: r=0.02, P=0.901). Conclusions The patients with SP exhibit the abnormal of whole brain WM structural network topological property and the node efficiencies of cortico-striato-thalamo circuitry are significantly reduced. Key words: Schizophrenia; White matter; Topological properties; Graph theoretical

Monitoring the Spread of Putaminal Gene Therapy for Parkinson Disease

The enzyme aromatic L-amino acid decarboxylase (AADC) is required to convert levodopa to dopamine; this enzyme is deficient in Parkinson disease (PD).