Establishment and clinical verification of brain template for analyzing 11C-CFT PET imaging data / 中华核医学与分子影像杂志

Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.

Distinguish mild cognitive impairment and normal cognitive change by β-amyloid PET imaging / 中华核医学与分子影像杂志

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.

Imaging study of β-amyloid deposits in preclinical Alzheimer′s disease patients in communities of Shanghai / 中华核医学与分子影像杂志

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.

Study of altered brain metabolism and connectivity in temporal lobe epilepsy / 中华核医学与分子影像杂志

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.

Application of 18F-AV45 PET imaging in subtle cognitive decline and mild cognitive impairment patients / 中华核医学与分子影像杂志

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.

Preoperative 11C-methionine PET imaging in glioma grading efficacy and its predictive value for IDH1 gene mutation status / 中华核医学与分子影像杂志

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.

Brain glucose metabolism network and connectivity in patients with somatoform disorders / 中华核医学与分子影像杂志

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 1000 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 (σ＞ 1).There were decreased tendency in normalized clustering coefficient and global efficiency,and increased tendency in normalized shortest path length in SFD patients,but without significant differences (P＞0.05).Compared to healthy controls,the betweenness centrality of left pallidum,left amygdala,left precuneus and right angular gyrus increased (permutation test,P＜0.05);the betweenness centrality of left middle temporal gyrus,right superior occipital gyrus decreased (permutation test,P＜0.05);the clustering coefficients of bilateral pallidum,bilateral thalamus,and left amygdala decreased (permutation test,P ＜ 0.05).Most changed Hub nodes (16/24) belonged to limbic system.Conclusion The changes of topological properties of brain glucose metabolic network in SFD patients including the decreased tendency of small-worldness and global efficiency,as well as the altered Hub nodes,may provide valid imaging evidences for brain dysfunction of somatization symptoms.

Brain glucose metabolism network and connectivity in patients with somatoform disorders / 中华核医学与分子影像杂志

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 (σ>1). There were decreased tendency in normalized clustering coefficient and global efficiency, and increased tendency in normalized shortest path length in SFD patients, but without significant differences (P>0.05). Compared to healthy controls, the betweenness centrality of left pallidum, left amygdala, left precuneus and right angular gyrus increased (permutation test, P<0.05); the betweenness centrality of left middle temporal gyrus, right superior occipital gyrus decreased (permutation test, P<0.05); the clustering coefficients of bilateral pallidum, bilateral thalamus, and left amygdala decreased (permutation test, P<0.05). Most changed Hub nodes (16/24) belonged to limbic system.@*Conclusion@#The changes of topological properties of brain glucose metabolic network in SFD patients including the decreased tendency of small-worldness and global efficiency, as well as the altered Hub nodes, may provide valid imaging evidences for brain dysfunction of somatization symptoms.

Quantification ofβcell mass using18 F-FP-(+)-DTBZ, a vesicular monoamine transporter type 2 radiotracer:A longitudinal study in type 1 diabetic rats / 中华内分泌代谢杂志

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.