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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.
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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.
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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.
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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.
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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.
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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.
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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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Objective To synthesize 18 F-DPA-714 and to study its labeling rate, radiochemical purity, stability and biological characteristics. Methods 18F-was reacted with K2CO3/K2.2.2 and then en-gaged in nucleophilic substitution with DPA-714. The crude product was purified by aluminum column and semi-preparation HPLC. The stability of 18 F-DPA-714 was identified in PBS and plasma. The lipid-water partition coefficient (LogP) was determined. Biodistribution analysis and microPET imaging were performed on mice and rats respectively. Results It took about 25 min for synthesizing 18 F-DPA-714, the radiochemi-cal yield was 31.6% (decay not corrected), and the radiochemical purity was ≥99%. The product re-mained stable within 4 h. The LogP of 18 F-DPA-714 was 2.71. Pharmacokinetics of 18 F-DPA-714 was more in line with the two compartment model, with the distribution half-life ( T1/2α) of 2.40 min and the elimina-tion half-life( T1/2β) of 69.15 min. 18 F-DPA-714 was quickly uptaken by tissues after the tail vein injection. It mainly distributed in the lungs, kidneys, and heart, with the radioactive uptake values of (17.85±7.52)%ID/g, (15.41±1.80) %ID/g and (10.56±0.94) %ID/g at 30 min post-injection, respectively. 18F-DPA-714 was mainly metabolized through the liver, and excreted by the kidneys. The uptake in bones was stable. PET dynamic scanning showed that 18 F-DPA-714 accumulated in the brain of aged rats and cleared slowly within 60 min. Conclusions 18 F-DPA-714 prepared in this study has high labeling rate, short synthesis time and small precursor dosage. It displays good biological distribution and blood-brain barrier permeability characteristics.
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Objective To synthesize 18 F-DPA-714 and to study its labeling rate, radiochemical purity, stability and biological characteristics. Methods 18F-was reacted with K2CO3/K2.2.2 and then en-gaged in nucleophilic substitution with DPA-714. The crude product was purified by aluminum column and semi-preparation HPLC. The stability of 18 F-DPA-714 was identified in PBS and plasma. The lipid-water partition coefficient (LogP) was determined. Biodistribution analysis and microPET imaging were performed on mice and rats respectively. Results It took about 25 min for synthesizing 18 F-DPA-714, the radiochemi-cal yield was 31.6% (decay not corrected), and the radiochemical purity was ≥99%. The product re-mained stable within 4 h. The LogP of 18 F-DPA-714 was 2.71. Pharmacokinetics of 18 F-DPA-714 was more in line with the two compartment model, with the distribution half-life ( T1/2α) of 2.40 min and the elimina-tion half-life( T1/2β) of 69.15 min. 18 F-DPA-714 was quickly uptaken by tissues after the tail vein injection. It mainly distributed in the lungs, kidneys, and heart, with the radioactive uptake values of (17.85±7.52)%ID/g, (15.41±1.80) %ID/g and (10.56±0.94) %ID/g at 30 min post-injection, respectively. 18F-DPA-714 was mainly metabolized through the liver, and excreted by the kidneys. The uptake in bones was stable. PET dynamic scanning showed that 18 F-DPA-714 accumulated in the brain of aged rats and cleared slowly within 60 min. Conclusions 18 F-DPA-714 prepared in this study has high labeling rate, short synthesis time and small precursor dosage. It displays good biological distribution and blood-brain barrier permeability characteristics.
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Objective To evaluate the parametric features of image textures on 18F-FDG PET/CT for the differentiation between malignant and benign pulmonary nodules and compare the diagnostic performance of these parameters with SUVmax.Methods 18F-FDG PET/CT images of 170 patients (102 males,68 females,age range:29-81 (mean 59)years) with pulmonary nodules were retrospectively evaluated.Eightynine pulmonary nodules (230 slices) were malignant and 81 (193 slices) were benign.The pulmonary nodules were contoured on CT images and mapped to the co-registered PET images.Thirteen parameters of textural features were extracted and SUVmax was measured.Logistic regression analysis was used to identify the significant texture parameters and create a regression model.The efficacy of the textural features and SUVmax to distinguish between malignant and benign pulmonary nodules was evaluated by ROC curve analysis.The textural features of squamous cell carcinoma and adenocarcinoma were compared via the Mann-Whitney u test.The sensitivity and specificity of the textural features and SUVmax for the differential diagnosis were compared with x2 test.Results Logistic regression model identified 4 textural features (skewness (β =1.7058),kurtosis (β =-1.0989),angular second moment (ASM,3 =-4.4140) and strength (β =0.5626) ; all P ＜ 0.05) to have significant correlation with the malignancy of lung nodules.The AUC of ROC curve was 0.775 (95％ CI0.732-0.819; P＜0.001) with the sensitivity of 89.6％ (206/230) and specificity of 50.8％ (98/193).ASM and strength had statistically significant differences between squamous cell carcinoma and adenocarcinoma [ASM:0.0303 (95％ CI 0.0392-0.0724) vs 0.0594 (95％ CI 0.0721-0.0947) ; strength:2.4714 (95％ CI 2.4632-4.1050) vs 1.5945 (95％ CI 1.9003-2.4652) ; u =3082.0 and 3115.0,both P＜0.01].The AUC of SUVmax-based diagnosis was 0.757 (95％ CI 0.711-0.802 ; P ＜ 0.001) with the sensitivity of 80.9 ％ (186/230) and specificity of 50.3 ％ (97/193) at a cut-off value of 2.5.The sensitivity of the textural features was superior to SUVmax in differentiating malignant from benign pulmonary nodules (x2 =6.903,P ＜ 0.01).Conclusions Image textural parametric features extracted from 18 F-FDG PET/CT are more sensitive to differentiate between malignant and benign pulmonary nodules compared to SUVmax.They might also be useful to discriminate between different pathological types of lung cancers.