1.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.
2.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.
3.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.
4.Distinguish mild cognitive impairment and normal cognitive change by β-amyloid PET imaging
Yue QIAN ; Mengjie WANG ; Junpeng LI ; Dan ZHOU ; Donglang JIANG ; Jianfei XIAO ; Shuhua REN ; Yihui GUAN ; Qi HUANG ; Qihao GUO ; Fang XIE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(2):65-69
Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.
5.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.
6.Imaging study of β-amyloid deposits in preclinical Alzheimer′s disease patients in communities of Shanghai
Mengjie WANG ; Shasha XU ; Donglang JIANG ; Junpeng LI ; Jianfei XIAO ; Shuhua REN ; Qi HUANG ; Yihui GUAN ; Xingmin HAN ; Lin HUANG ; Keliang CHEN ; Fang XIE ; Qihao GUO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(1):20-24
Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.
7.18F-MK6240 PET imaging of tau protein in Alzheimer′s disease and cognitive correlation analysis
Weiyi WANG ; Ying WANG ; Mengjie WANG ; Jie WANG ; Junpeng LI ; Donglang JIANG ; Jianfei XIAO ; Shuhua REN ; Qi HUANG ; Kun HE ; Yihui GUAN ; Qihao GUO ; Binyin LI ; Fang XIE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(10):583-587
Objective:To investigate the tau deposition pattern in Alzheimer′s disease (AD) and its correlation with cognition by 18F-MK6240 PET imaging. Methods:From August 2021 to February 2022, 46 elderly people over 55 years old (16 males, 30 females; age (68.9±7.7) years) were included from outpatient and community in Shanghai. Structural brain MRI, β-amyloid (Aβ) PET imaging, tau-PET imaging and comprehensive neuropsychological tests batteries were conducted. The subjects were divided into AD group ( n=16) and normal cognition (NC) group ( n=30) according to the 2018 National Institute on aging and Alzheimer′s Association (NIA-AA) diagnostic criteria. Quantitative analysis was conducted to investigate the tau deposition pattern in AD after preprocessing 18F-MK6240 PET images with MRI images. SUV ratio (SUVR) of brain regions such as entorhinal cortex, hippocampus, parahippocampal gyrus, amygdala, insular lobe, frontal lobe, precuneus, occipital lobe, thalamus and putamen were analyzed, with cerebellum as reference region. The differences of tau deposition in brain regions between AD and NC groups were analyzed by independent-sample t test. The associations between SUVR and Mini-Mental State Examination (MMSE) score and Montreal Cognitive Assessment-Basic (MoCA-B) score were analyzed by Pearson correlation analysis. Results:AD displayed a significant tau deposition in frontal lobes, temporal lobes and parietal lobes compared with NC. SUVR of brain regions in AD group were higher than those in NC group ( t values: 3.37-9.61, all P<0.05). SUVR in brain regions were negatively correlated with MMSE score ( r values: from -0.735 to -0.350, all P<0.05) and MoCA-B score ( r values: from -0.723 to -0.367, all P<0.05). Conclusion:18F-MK6240 PET can demonstrate the tau deposition in the brain of AD patients, and the tau deposition is related to cognitive function.
8. 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 (