1.Study of altered brain metabolism and connectivity in temporal lobe epilepsy
Yijing CHEN ; Qi HUANG ; Rui FENG ; Weiqi BAO ; Donglang JIANG ; Junpeng LI ; Jianfei XIAO ; Fang XIE ; Fengchun HUA ; Yihui GUAN ; Shuhua REN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(11):661-665
Objective:To explore the abnormal brain metabolic pattern and connectivity in temporal lobe epilepsy (TLE) patients.Methods:18F-FDG PET images of 75 patients diagnosed as drug resistant unilateral TLE from January 2014 to December 2016 in Huashan Hospital of Fudan University were collected retrospectively, including 41 (22 males, 19 females, age (28.4±8.7) years) left TLE (LTLE) and 34 (13 males, 21 females, age (28.5±8.8) years) right TLE (RTLE). Forty-four healthy controls (24 males, 20 females, age (31.2±6.2) years) were also enrolled. The cerebral glucose metabolism in TLE patients and the controls were analyzed with statistical parametric mapping (SPM) 12. The brain connectivity based on glucose metabolism were analyzed with bilateral hippocampus and amygdala as seeds. Permutation test with 1 000 permutations was used to analyze data. Results:Compared to control group, in both LTLE and RTLE groups, hypometabolism was found in affected hippocampus, amygdala, insula and temporal gyrus and hypermetabolism was observed in health hippocampus, parahippocampal gyrus, amygdala, lenticular nucleus and thalamus. In addition, hypometabolism was also found in affected superior/middle frontal gyrus and hypermetabolism was also found in bilateral frontal-orbital gyrus, bilateral cerebellum, affected lenticular nucleus and thalamus in LTLE group. In both TLE groups, affected seeds exhibited increased connectivity with affected superior frontal gyrus, lingual gyrus, fusiform gyrus, superior/middle temporal gyrus and temporal pole (all P<0.05); affected seeds exhibited increased connectivity with health superior frontal gyrus ( P=0.005), lingual gyrus ( P=0.018) and transverse temporal gyrus ( P=0.016) in RTLE group in addition. Besides, affected seeds exhibited decreased connectivity with bilateral default mode network (DMN) (all P<0.05), affected caudate nucleus ( P=0.015) and health thalamus ( P=0.008), in a uniform distribution pattern in LTLE group, and with bilateral cerebral cortex in an irregular distribution pattern in RTLE group (all P<0.05). In LTLE group, health seeds exhibited more increased connections with superior ( P=0.005)/middle frontal gyrus ( P=0.042), health hippocampus ( P=0.038), parahippocampal gyrus ( P=0.019), amygdala ( P=0.038), posterior cingulate gyrus ( P=0.004), and bilateral fusiform gyrusand ( P=0.048) compared with RTLE group; while, in RTLE group, health seeds exhibited more decreased connections with health superior ( P=0.047), inferior frontal gyrus ( P<0.001), orbital frontal gyrus ( P<0.001) and rectus gyrus ( P=0.016) compared with LTLE group. Conclusion:Altered brain glucose metabolism and connectivity pattern are found and will elucidate the underlying metabolic pattern of TLE.
2.Clinical analysis of 19 cases with granulomatosis with polyangiitis complicated with hypertrophic cranial pachymeningitis
Lijuan GOU ; Qingjun WU ; Li WANG ; Min QIAN ; Hua CHEN ; Wenjie ZHENG ; Yan ZHAO ; Fengchun ZHANG ; Xiaofeng ZENG
Chinese Journal of Rheumatology 2020;24(1):13-17
Objective:To discuss the clinical features and treatment of 19 patients with granulomatosis with polyangiitis (GPA) complicated with hypertrophic cranial pachymeningitis (HCP).Methods:The clinical features of 19 patients diagnosed with GPA complicated with HCP in Peking Union Medical College Hospital were retrospectively analyzed.Results:Among the 315 patients with GPA, 19 (12 males, 7 females, with) were diagnosed with HCP at Peking Union Medical College Hospital. The median age was 57 (19-64) years. In the neurological manifestations per se, all patients had headache, 16 patients had cerebral involvement, which included 8 cases at the frontal area, 8 cases at the temporal area, 8 cases at the skull base area (4 cases with parasellar involvements including 3 cases with cavernous sinus involvement and 2 cases with orbital involvement), 6 cases of tentorium involvement, 2 cases of cerebral palsy, 1 case of calvarium, 1 case of occipital, and 1 case with combined spinal pachymeningitis, respectively. In systemic manifestations, 10 patients had fever, 8 patients had weight lose, 4 patients had lung involvement, 3 patients had kidney involvement, 16 patients had nasosinusitis, 10 patients had tympanitis, and 16 patients had localized GPA. The laboratory tests showed that 15 patients had positive anti-neutrophil cytoplasmic antibodies (ANCA), including 8 cases with positive proteinase 3 (PR3)-ANCA and 6 cases with positive myeloperoxidase (MPO)-ANCA. Sixteen patients had lumbar puncture examination, 9 cases had elevated cerebrospinal pressure, 10 cases had elevated level of protein in cerebrospinal fluid. Nineteen patients were treated with glucocorticoids (12 patients accepted pulse therapy) and immunosuppressive agents. Twelve patients were treated with intrathecal injections of dexamethasone combined with or without Methotrexate (MTX). All 19 patients were improved.Conclusion:HCP, as a rare but serious manifestation of GPA, is not rare in active cases and should be intensively treated.
3.Preoperative 11C-methionine PET imaging in glioma grading efficacy and its predictive value for IDH1 gene mutation status
Weiyan ZHOU ; Fengchun HUA ; Jianfei XIAO ; Ming LI ; Yuhua ZHU ; Tao HUA ; Yihui GUAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(3):153-158
Objective:To assess the preoperative 11C-methionine ( 11C-MET) PET imaging in glioma grading efficacy and its predictive value for isocitrate dehydrogenase enzyme 1 (IDH1) gene mutation status. Methods:A total of 118 glioma cases (70 males, 48 females; median age 45 years, age range: 10-71 years; Ⅱ grade 65 cases, Ⅲ grade 34 cases, Ⅳ grade 19 cases) received 11C-MET PET imaging in PET Center of Huashan Hospital from February 2012 to November 2017 were retrospectively analyzed. Lesion-based semi-quantitative analysis was conducted on the 11C-MET imaging. Maximum standardized uptake value (SUV max), peak standardized uptake value (SUV peak), tumor-to-background ratio (TBR; SUV max in lesion/mean standardized uptake value (SUV mean) in normal contralateral cortex) were calculated. Independent-sample t test and one-way analysis of variance were applied to assess the differentiating efficacy of 11C-MET PET imaging for different glioma groups. Based on IDH1 immunohistochemical staining results, predictive efficacy of 11C-MET PET diagnostic parameters on IDH1 mutation status in glioma patients was further analyzed with receiver operating characteristic (ROC) curve analysis. Results:Low-grade glioma (LGG; grade Ⅱ) group showed significant differences from high-grade glioma (HGG; grade Ⅲ-Ⅳ) group in SUV max(2.458±1.100 vs 3.828±1.540; t=5.624, P<0.01), SUV peak (2.160±0.991 vs 3.261±1.319; t=5.175, P<0.01) and TBR (2.283±0.942 vs 3.434±1.395; t=5.328, P<0.01). SUV max (2.458±1.100, 3.591±1.611 and 4.251±1.343; F=17.67, P<0.01), SUV peak(2.160±0.991, 3.040±1.335 and 3.656±1.225; F=15.48, P<0.01) and TBR (2.283±0.942, 3.010±1.242 and 4.192±1.358; F=22.73, P<0.01) were different in grade Ⅱ, Ⅲ and Ⅳ glioma subgroups. SUV max, SUV peak and TBR all showed significant differences between grade Ⅱ and grade Ⅲ gliomas, grade Ⅱ and grade Ⅳ gliomas, and there were also statistical differences between grade Ⅲ and grade Ⅳ glioma with TBR (all P<0.01). SUV max indicated the best single-parameter prediction performance (area under curve (AUC) =0.808, z=7.193, P<0.01), while the SUV max + SUV peak showed the best performance (AUC=0.852, z=9.115, P<0.01). In the subgroup of grade Ⅱ ( n=55), TBR of patients with IDH1 gene mutation ( n=41) was lower than that of patients with IDH1 wild-types ( n=14; 2.152±0.759 vs 2.793±1.208; t=2.326, P=0.02), while TBR of those with oligodendrogenic components ( n=26) was higher than that of patients with IDH1 gene mutation only ( n=18; 2.383±0.825 vs 1.854±0.478; t=2.447, P=0.02). Conclusions:Preoperative semi-quantitative parameters (SUV max, SUV peak, TBR) of 11C-MET brain PET imaging have satisfactory grading discrimination performance for glioma patients. SUV max is the best predictor for IDH1 mutation as a single parameter, while SUV max + SUV peak showed the most optimized predictive ability. The oligodendrogenic components in glioma can increase the uptake of 11C-MET, which may affect the effectiveness of 11C-MET in determining glioma grade to some extent.
4.Application of 18F-AV45 PET imaging in subtle cognitive decline and mild cognitive impairment patients
Shuhua REN ; Qi HUANG ; Jingchao HU ; Donglang JIANG ; Jianfei XIAO ; Qihao GUO ; Fang XIE ; Fengchun HUA ; Yihui GUAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(4):196-200
Objective:To investigate the correlations between cerebral β-amyloid (Aβ) deposition assessed by 18F-florbetapir (AV45) PET imaging and clinical cognitive symptoms in patients with subtle cognitive decline (SCD) and mild cognitive impairment (MCI). Methods:Data of twenty-four patients (11 males, 13 females, age: (63.2±7.6) years) diagnosed as SCD ( n=15) or MCI ( n=9) from December 2018 to March 2019 in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital were collected prospectively. All patients underwent 18F-AV45 PET imaging, brain MRI T 1 scan and Mini-Mental State Examination (MMSE) within two weeks. 18F-AV45 PET images were analyzed visually (positive, mild positive, negative). After being pretreated according to the MRI, 18F-AV45 PET images were analyzed semi-quantitatively by calculating the standardized uptake value ratio (SUVR) of Aβ deposition in 8 regions of interest (ROIs; frontal lobe, lateral parietal lobe, lateral temporal lobe, medial temporal lobe, occipital lobe, basal ganglia, posterior cingulate and precuneus), with cerebellar gray matter as the reference. Partial correlation coefficients between regional SUVRs and MMSE score were calculated. Results:18F-AV45 PET imaging showed that 16 patients with positive results and 8 patients with mild positive results. MMSE score of 24 patients was 28.2±2.0, and the SUVR was 0.93-1.87. Correlation analysis revealed that Aβ deposition in frontal cortex ( r=-0.432), posterior cingulate lobe ( r=-0.434) and precuneus ( r=-0.418) was negatively correlated with MMSE score (all P<0.05); and no significant correlations between SUVR and MMSE in other brain regions were found ( r values: from -0.412 to -0.110, all P>0.05). Conclusion:18F-AV45 PET imaging can noninvasively detect brain Aβ deposition in patients, and can effectively reflect the clinical cognitive status of patients with SCD and MCI to a certain extent.
5. Brain glucose metabolism network and connectivity in patients with somatoform disorders
Zhiwei PAN ; Jianfei XIAO ; Qi HUANG ; Donglang JIANG ; Shuhua REN ; Yihui GUAN ; Fang XIE ; Daliang SUN ; Fengchun HUA
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(1):6-10
Objective:
To observe the alteration of brain glucose metabolic network in patients with somatoform disorders (SFD).
Methods:
18F-fluorodeoxyglucose (FDG) PET images of 18 SFD patients (10 males, 8 females; age: (39.5±12.0) years; illness duration: (3.67±3.20) years) and 21 matched healthy controls (13 males, 8 females; age: (43.9±8.4) years) in Huashan Hospital of Fudan University from October 2011 to December 2012 were enrolled to construct the brain glucose metabolic networks for 2 groups (SFD group, control group) respectively. Then the global network properties (normalized clustering coefficient, normalized shortest path length, small-worldness and global efficiency) and local parameters (clustering coefficient and betweenness centrality of the node) were calculated using the graph theory. Differences between 2 groups were compared by permutation test with 1 000 permutations. The top 20% (18/90) were classified as Hub nodes based on the results of clustering coefficient and betweenness centrality of the node.
Results:
Small-worldness of SFD patients was similar to that of healthy controls (
6.Quantification ofβcell mass using18 F-FP-(+)-DTBZ, a vesicular monoamine transporter type 2 radiotracer:A longitudinal study in type 1 diabetic rats
Jianfei XIAO ; Donglang JIANG ; Shuhua REN ; Qi HUANG ; Fang XIE ; Yihui GUAN ; Fengchun HUA
Chinese Journal of Endocrinology and Metabolism 2019;35(6):494-498
Objective The aim of this study was to investigate the possibility of type 2 vesicular monoamine transporter molecular probe,18 F-FP-(+)-DTBZ, in the monitoring of total islet β cell mass in animal models. Methods Two groups of Wistar rats were included in this study. In the type 1 diabetes group ( n = 6 ) , the streptozotocin ( STZ) was intraperitoneally injected at a dose of 65 mg/kg, and the control group ( n= 6 ) was likewisely injected with an equal volume of saline, Micro- positron emission tomography ( PET )/ computed tomography ( CT) imaging was performed at these rats post injection of18 F-FP-(+)-DTBZ at 0. 5, 1, 4, 6, and 12 months after STZ or saline injection, bodyweight and glucose level were also measured. Results The average standardized uptake values ( SUV) in the pancreas in the type 1 diabetes rats were decreased significantly than that of the control group at 0.5, 1, and, 4 months ( P<0.05) , and there was no significant difference at 6th and 12th months ( P>0.05) post injection of STZ and saline. Fasting blood glucose positively correlated with pancreatic SUV in the two groups at 0.5, 1, and 4 months (P<0.05) post injection of STZ and saline. Conclusion 18F-FP-(+)-DTBZ PET imaging is a promising method for dynamic monitoringβcell mass in type 1 diabetic rats.
7.Analysis of the relationship between health-related quality of life (primary biliary cholangitis-40) and clinical presentations of patients with primary biliary cholangitis
Shuo ZHANG ; Li WANG ; Liling ZHAO ; Jinlei SUN ; Zhilei CHEN ; Yihan CAO ; Tihong SHAO ; Yunjiao YANG ; Hua CHEN ; Yongzhe LI ; Fengchun ZHANG
Chinese Journal of Rheumatology 2018;22(12):798-801
Objective To investigate the health related quality of life score [primary biliary cholangitis (PBC)-40] in patients with PBC,and the relationship between PBC-40 and clinical presentations.Methods The PBC-40 score and clinical presentations in PBC patients (n=65) were adapted in this study.Patients were divided into the untreated group and the treated group,and the treated group was further divided into ursodesoxycholic acid (UDCA) response group and UDCA non-response group.PBC-40 scores of different groups were analyzed by t-test and the relationship between PBC-40 and clinical presentations were analyzed with Pearson's test.Results Dimensions of PBC-40 scores of this group of patients were as follows:symptoms were (15.8±4.1) points,itch was (4.9±2.8) points,atigue was (23.8±8.9) points,cognitive dysfunction score was (11.4±4.7) points,social activity score was (17.0±7.5) points,and the emotion score was (6.5±3.1) points.The untreated group had higher emotion scores than the treated group (t=2.024,P=0.045).Compared with the UDCA response group,UDCA non-response group had higher scores in cognitive,social and emotion dimension (t =2.126,2.309,2.062,respectively,P=0.039,0.025,0.045,respectively).Itch score was significantly correlated with total bilirubin (TBil),direct bilirubin (DBil),alkaline phosphatase (ALP) and total bile acid (TBA) (r=0.349,0.345,0.324,0.427,respectively,P<0.01),while the social scores were correlated with TBil,DBil,aspartate aminotransferase (AST) and TBA (r=0.361,0.383,0.316,0.331,P<0.01) and emotion scores were associated with ALT,TBil,GGT,ALP,AST and TBA (r=0.332,0.430,0.265,0.326,0.297,0.353,P<0.05).ConclusionPBC-40 can be used as a health-related quality of life assessment for PBC patients inChinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health quality of life in PBC patients.Conclusion PBC-40 can be used as a health-related quality of life assessment for PBC patients in Chinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health related quality of life in PBC patients.
8.Expression of programmed death-1 in CD8+T lymphocyte and Treg lymphocyte in patients with primary biliary cholangitis
Shuo ZHANG ; Li WANG ; Liling ZHAO ; Jinlei SUN ; Zhilei CHEN ; Tihong SHAO ; Hua CHEN ; Yunjiao YANG ; Yongzhe LI ; Fengchun ZHANG
Chinese Journal of Rheumatology 2018;22(8):532-536
Objective To investigate the expression of programmed death receptor-1 (PD-1) in CD8+ T cells and FoxP3+CD4+ cells in patients with primary biliary cholangitis (PBC).Methods The peripheral blood and clinical data of 69 PBC patients in Peking Union Medical College Hospital and 58 health controls (HC) were collected.They were divided into initial treatment group and follow-up group according to whether they were treated or not.Patients in the treatment group were further divided into the refractory group and stable group according to treatment response.Flow cytometry was used to detect the expression of PD-1 in CDS+T cells and FoxP3+CD4+ cells.T-test and Person correlation analysis were used for data analysis.Results The PD-1 expression in peripheral blood mononuclear cells (PBMCs) of 69 PBC patients (12±9)% was lower than that of HC (20±12)% (t=-3.687,P<0.01).The percentage of PD-1+ in FoxP3+ CD4+T cells was significantly increased in PBC (5.6±3.7)% than HC (7.4±2.4)% (t=2.048,P<0.01).The proportion of CD8+T cells,PD-1 expression in CD8+T cells and the proportion of FoxP3+CD4+ cells weren't correlated with clinical parameters (P>0.05).There was a negative correlation between the expression of PD-1 cells in FoxP3+CD4+ cells and GLOBE score (r=-0.307,P<0.05).Conclusion The expression of PD-1 in peripheral CD8+T lymphocytes of PBC patients is lower than that of HC,and decreases more significantly in the refractory group.The expression of PD-1 on FoxP3+CD4+T cells is higher than that in HC,and is negatively correlated with the prognostic GLOBE score.It suggests that PD-1/PD-L1 pathway participates in the immune mechanism of PBC.
10.Evaluation of β-cell mass in type 2 diabetic patients with 18F-FP-(+)-DTBZ,a vesicular monoamine transporter type 2 molecular probe
Donglang JIANG ; Yanyan KONG ; Xiuhong LU ; Ming LI ; Weiyan ZHOU ; Fengchun HUA ; Fang XIE ; Yihui GUAN
Chinese Journal of Endocrinology and Metabolism 2018;34(8):638-642
Objective The aim of this study was to evaluate theβ-cell mass ( BCM) in patients with type 2 diabetes mellitus( T2D) by PET/CT using [ 18 F]-FP-(+)-DTBZ, which is a vesicular monoamine transporter type 2 molecular probe. The feasibility of pancreatic head, body and tail as the target area was investigated for evaluation of the BCM in T2D. Methods 15 subjects ( 8 with T2D, and 7 as control) were involved in this study with 20 min static PET imaging at 40 min post injection of [ 18 F]-FP-(+)-DTBZ. The volume of interest ( VOIs) of pancreatic head, body and tail were drawn and quantitatively assessed. Spleens were collected as reference tissue for SUVR calculation. Results SUVR in the pancreatic head ( SUVR=1.72 ± 0.47) and pancreatic body, tail ( SUVR=1.85 ± 0.41) in T2D group was no significant difference, and no significant difference was observed in the pancreatic head (SUVR=2.54±0.57) and pancreatic body, tail(SUVR=2.73±0.41) in control group as well. In T2D group, a significant decreased SUVR was found in pancreatic head (P=0.0088) and pancreatic body and tail (P=0.0012) compared with controls. Conclusion The VMAT2 molecular probe [ 18 F]-FP-(+)-DTBZ can be used to evaluate BCM in patients with T2D.

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