Multi-centre clinical trials on PET/CT brain imaging are complex to organize and require careful co-ordination and management. This article describes considerations, which are necessary when designing and starting a multi-centre clinical trial on PET/CT brain imaging, based on guidelines and multi-center clinical brain imaging studies, providing references for further studies.

Objective:To explore the application of OTSU-based self-attenuation correction PET (sacPET) reconstruction technology in 18F-florbetapir (AV45) imaging. Methods:From November 2018 to December 2019, 7 confirmed Alzheimer′s disease (AD) patients (4 males, 3 females, age (69.6±4.5)years) and 3 healthy controls (HC; 1 male, 2 females, age (68.0±4.6) years) were recruited prospectively for 18F-AV45 PET imaging in the First Affiliated Hospital of Sun Yat-Sen University. Original data collected by PET acquisition was processed with sacPET reconstruction and then compared with standard PET images by visual analysis and semi-quantitative analysis. Fisher exact test, Kappa test and Pearson correlation analysis were used to analyze data. Results:In HC group and AD group, the radioactive distribution showed by sacPET images and that by standard PET images were similar, and the contrast of gray-white matter in sacPET images was weaker than that in standard PET images. Moreover, the positive uptake area of the cortex in the AD group was smaller than that in standard PET images. Visual analysis showed 19 positive regions in sacPET images and 22 in standard PET images, with no statistical difference of positive rates of the sub-regions in the cortex between the two PET images (all P>0.05), and the overall consistency of 88.00% (44/50; Kappa=0.75 (95% CI: 0.57-0.94), P<0.05). Semi-quantitative analysis showed that the standardized uptake value ratio (SUVR) of frontal lobe and cingulate gyrus measured by sacPET was lower than that measured by standard PET (0.93±0.06 vs 0.96±0.06 and 0.99±0.04 vs 1.01±0.04; t values: 5.30 and 5.10, both P<0.01), while SUVR of parietal lobe, temporal lobe and occipital lobe measured by sacPET was higher than that measured by standard PET (0.78±0.08 vs 0.68±0.07, 0.97±0.07 vs 0.91±0.08 and 0.94±0.11 vs 0.71±0.12; t values: 6.27, 7.36 and 16.90, all P<0.01). The overall SUVR of sacPET images was significantly correlated with the standard PET images ( r=0.75, P<0.001). Conclusion:For 18F-AV45 imaging, sacPET reconstruction technology can obtain reliable and effective PET images without CT data, but its accuracy and precision still need to be improved.

Objective:To explore the relationship between vesicular monoamine transporter 2(VMAT2) density in the striatum and the non-motor symptoms(NMSs) in patients with Parkinson′s disease(PD).Methods:From December 2018 to December 2019, 29 normal controls (16 males, 13 females, age: (48.8±14.2) years), 31 patients with PD at the Hoehn-Yahr (mH-Y) Ⅱ stage (16 males, 15 females, age: (53.4±8.5) years) and 36 patients with PD at mH-Y Ⅲ stage (19 males, 17 females, age: (63.1±8.2) years) in the First Affiliated Hospital of Sun Yat-sen University were prospectively enrolled in this study. All subjects underwent 18F-fluoropropyl-(+ )-dihydrotetrabenazine( 18F-FP-(+ )-DTBZ, 18F-AV133) PET/CT imaging, then the specific uptake ratios (SURs) of striatal subregions were measured with the occipital cortex as the reference background region. The clinical data, laboratory data and imaging results were collected. The NMSs of each patient were evaluated with Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), Parkinson′s Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), Parkinson′s Disease Quality of Life Questionnaire (PDQL) and Non-Motor Symptoms Scale (NMSS). The independent-sample t test and one-way analysis of variance (the least significant difference t test) were used to compare data differences. Finally, the association of the striatal SURs with the clinical symptom scores were evaluated with Pearson correlation analysis and multivariable stepwise regression analysis. Results:Significant differences were found in depression (3.51±1.34 vs 11.36±3.87), anxiety (2.35±1.45 vs 6.00±3.32), sleep disorder (132.90±12.26 vs 110.34±19.69) and life quality (7.58±3.37 vs 24.01±10.15) scores between the mH-Y stage Ⅱ and the stage Ⅲ patients ( t values: from -10.573 to 5.439, all P<0.05), while cognitive scores did not differ significantly between the 2 PD groups ( t=1.067, P>0.05). Compared with healthy control group (1.28±0.22), the PD groups displayed a more marked decrease of SURs in the bilateral putamen and in the caudate nucleus (0.65±0.16 and 0.31±0.14; F=83.11, P<0.05), and the SURs of patients at stage Ⅱ were higher than those of the patients at stage Ⅲ ( t=9.116, P<0.05). NMSs scores of PD patients, with the exception of cognition scores, were correlated with striatal SURs ( r values: from -0.647 to -0.426, all P<0.05). Regression analysis showed that total striatum SURs was the best predictor of PDSS and NMSS scores ( R2 values: 0.234, 0.378, both P<0.001), while contralateral caudate nucleus SURs were best predictor of HAMD scores ( R2=0.402, P<0.001). The SURs of contralateral putamen were best variables for predicting HAMA scores ( R2=0.204, P<0.001). Conclusion:The correlation between the decreased striatal VMAT2 and a broad spectrum of NMSs in patients with PD is established, suggesting that the defect in dopamine supply may be an early abnormality promoting mechanisms leading to the development of NMSs in PD.

Objective:To compare the application of 13N-NH 3, 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) PET/CT imaging in the diagnosis and evaluation of suspected cerebral glioma. Methods:From September 2010 to December 2017, ninety patients (54 males, 36 females; age: (40.0±14.0) years) in the First Affiliated Hospital of Sun Yat-sen University with suspected glioma based on clinical diagnosis, who underwent 13N-NH 3, 11C-MET and 18F-FDG PET/CT imaging, were prospectively enrolled in the study. All patients were confirmed by histology or clinical and radiological follow-up. Images were interpreted by visual evaluation (higher radioactive uptake in lesions than that in the contralateral normal brain parenchyma was considered as positive (+ ), equal/lower were considered as negative (-)) and semi-quantitative analysis (the maximum standardized uptake value (SUV) of lesion (L) to the mean SUV of normal white matter (WM) (L/WM ratio)). Receiver operating characteristic (ROC) curve analysis was used and the area under curves (AUCs) were calculated and compared. The diagnostic efficacies of 3 imaging methods and the combination for diagnosing gliomas and the abilities to differentiating high-grade gliomas (HGG) and low-grade gliomas (LGG) were compared. Results:In 90 patients, 30 HGG, 27 LGG, 10 non-glioma brain tumors and 23 non-neoplastic lesions (NNL) were diagnosed. On visual evaluation, the sensitivities for differentiating tumors from NNL were 62.7%(42/67), 94.0%(63/67) and 35.8% (24/67) for 13N-NH 3, 11C-MET and 18F-FDG PET/CT respectively, while the specificities were 95.7%(22/23), 56.5% (13/23) and 65.2% (15/23), and the accuracies were 71.1%(64/90), 84.4%(76/90) and 43.3% (39/90). Taking the metabolic patterns of + /+ /+ , + /+ /- and + /-/- ( 11C-MET/ 13N-NH 3/ 18F-FDG) as the diagnosis standard of tumor lesions, the specificity and accuracy of the combined method increased to 73.9%(17/23) and 88.9%(80/90) with the sensitivity remaining the same (94.0%, 63/67). ROC curve analysis (L/WM) showed that the sensitivity, specificity and AUC were 64.2%(43/67), 100%(23/23) and 0.819 for 13N-NH 3 PET/CT, and 89.6%(60/67), 69.6%(16/23) and 0.840 for 11C-MET PET/CT ( z=-0.316, P>0.05). The accuracy for differentiating high and low grade glioma were 86.0% (49/57), 87.7%(50/57) and 93.0%(53/57) for 13N-NH 3, 11C-MET and 18F-FDG PET/CT, with the AUC of 0.896, 0.928 and 0.964, respectively ( z values: -0.554 to 1.334, all P>0.05). Conclusions:13N-NH 3 PET/CT imaging has remarkably high specificity but low sensitivity for the differentiation of brain tumors from NNL. 11C-MET PET/CT imaging was found to be highly useful for detection of brain tumors. However, like 18F-FDG, high MET uptake is frequently observed in some NNL. 13N-NH 3, 11C-MET and 18F-FDG PET/CT imaging all appear to be valuable for evaluating the histological grade of gliomas, and the combination of them is more useful for the accurate diagnosis of glioma.

Objective To investigate the application and value of entacapone in 6-18F-fluoro-L-dopa (18F-DOPA) PET/CT imaging on Parkinson's disease (PD).Methods From July 2016 to September 2017,44 PD patients (24 males,20 females,age:(51.3±11.0) years) and 14 healthy volunteers (7 males,7 females,age:(57.6± 14.4) years) who underwent 18F-DOPA PET/CT imaging were enrolled.They were divided into 4 groups:PD1 group with entacapone treatment (n=24);PD2 group without entacapone treatment (n=20);healthy control group with entacapone treatment (HC1,n=6);healthy control group without entacapone treatment (HC2,n =8).The striatal-to-occipital ratio (SOR) was calculated.Two-sample t test and receiver operating characteristic (ROC) curve analysis were used to analyze the data.Results The striatum was more clear and the uptake of cerebral cortex decreased significantly in PD1 and HC1 groups.The SOR of contralateral anterior putamen,posterior putamen and caudate nucleus in PD1 group were 15％,14％ and 15％ higher (t values:2.92,3.11,2.49,all P＜0.05) than those in PD2 group,and SOR of ipsilateral anterior putamen,posterior putamen and caudate nucleus in PD1 were 17％,21％ and 17％ higher (t values:2.90,3.56,3.00,all P＜0.05).SOR of left anterior putamen,posterior putamen and caudate nucleus in HC1 group were improved 29％,35％ and 27％ (t values:3.64,3.48,4.48,all P＜0.05) compared to those in HC2 group,and SOR of right anterior putamen,posterior putamen and caudate nucleus in HC1 group were improved 29％,28％ and 29％ (t values:2.92,2.73,3.61,all P＜0.05).The area under curve (AUC) for SOR of the left anterior and posterior putamen and the right posterior putamen in subjects with entacapone treatment were 0.999,0.999 and 0.972,which were far greater than 0.865,0.889 and 0.848 (z values:3.24,3.03,2.77,all P＜0.01) in those without entacapone treatment.The AUC for SOR of the right anterior putamen,the left caudate nucleus and the right caudate nucleus subjects with entacapone treatment were 0.927,0.941 and 0.906,respectively,which were also significantly greater than 0.754,0.766 and 0.696 (z values:2.01,2.36,2.17,all P＜0.05) in subjects without entacapone treatment.Conclusion Entacapone can increase the uptake of 18F-DOPA in the striatum of patients with PD,and it can improve the efficiency of 18F-DOPA to distinguish patients with PD from normal people.

Objective To investigate the clinical values of L-6-18 F-fluoro-3,4-dihydroxyphenylala-nine ( 18 F-DOPA) PET in the diagnosis and severity assessment of early-stage Parkinson's disease ( PD) . Methods Thirty-eight patients (24 males, 14 females; age:34-74 years) with early-stage PD (Hoehn-Yahr ( H-Y) staging:1-2) and 5 age-matched healthy volunteers ( all males;age:45-65 years) from July 2016 to March 2017 were included and underwent 18 F-DOPA PET scan in this retrospective study. The stria-tal-to-occipital ratio ( SOR) was calculated and compared between PD patients and healthy volunteers. The unified PD rating scale ( UPDRS) Ⅲ score and H-Y staging were used to evaluate the clinical symptoms. Two-sample t test and Pearson correlation analysis were used. Results In the control group, 18 F-DOPA SORs in bilateral putamen and caudate nucleus were 2.50±0.24 and 2.61±0.23, respectively. In PD group, the SORs of ipsilateral and contralateral putamen nucleus were 2.02±0.27 and 1.80±0.26 respectively, lower than those in the control group ( t values:-4.006,-5.440, both P<0.01) . The SORs of ipsilateral and contralater-al caudate nucleus were 2.16±0.32 and 2.08±0.28 respectively, lower than those in the control group ( t val-ues:-2.990,-4.047, both P<0.01). The SORs of contralateral putamen and caudate nucleus were signifi-cantly lower than those of the ipsilateral striatum respectively (t values:-6.431,-3.837, both P<0.01). Fur-thermore, the SORs in the striatum (putamen and caudate nucleus) were negatively correlated with UPDRSⅢscore, H-Y staging, and duration of disease (r values:from-0.526 to-0.369, all P<0.05). Conclusions 18F-DOPA PET can reflect the changes in the striatum neurons, and it may be an important method in the diag-nosis and assessment of early-stage PD patients.

Objective To validate the reproducibility of abnormal cerebral metabolic characteristics in PD patients from different medical centers using 18F-FDG PET imaging.Methods A total of 108 subjects who were referred for resting-state brain 18 F-FDG PET imaging were retrospectively reviewed.Thirtythree PD patients (15 males,18 females,age:38-79 years) and 33 age-matched healthy controls (15 males,18 females,age:40-77 years) underwent evaluation at Shanghai Huashan Hospital Affiliated to Fudan University.Seventeen PD patients (10 males,7 females,age:44-74 years) and 17 age-matched healthy controls (6 males,11 females,age:42-67 years) underwent evaluation at the First Affiliated Hospital of Sun Yat-sen University.SPM was used to investigate the cerebral metabolic characteristics of the patients with two-sample t test.Statistically significant voxels were obtained by using familywise error rate (FWE;P＜0.05).Two sets of PD patients with abnormal glucose metabolism of brain regions were obtained and the cerebral metabolic characteristics were compared.Results Regarding the PD patients from Shanghai Huashan Hospital,the features of cerebral glucose metabolism by SPM analysis were demonstrated as follows:increased metabolism was found in the region of pons,cerebellum,thalamus,putamen and pallidum,while decreased metabolism was displayed in the region of parietal lobe and occipital lobe.The increased regions referred to 8 110 voxels and decreased regions referred to 2 810 voxels (P＜0.05).The similar metabolic pattern was found in PD patients from the First Affiliated Hospital of Sun Yat-sen University.The increased metabolism was shown in the regions of pons,cerebellum,thalamus,putamen and pallidum,and referred to 15 573 voxels.The metabolism-decreased regions included parietal lobe,occipital lobe and frontal lobe,and referred to 3 945 voxels (P＜0.05).Conclusions 18F-FDG PET/CT imaging results demonstrate similar metabolic pattern in PD patients from different medical centers,in whom the metabolism-increased regions are found in the pons,cerebellum,thalamus and pallidum and decreased regions were demonstrated in the parietal lobe and occipital lobe.The reproducibility from 18F-FDG PET/CT imaging provides reliable evidence for the multi-center study in the differential diagnosis of PD.

Objective To evaluate the biodistribution and radiation-absorbed doses of main organs in healthy people with 13 N-ammonia.Methods Five healthy volunteers underwent whole-body PET and CT scans after injection of 666-814 MBq of 13 N-ammonia.The serial dynamic emission images of each healthy volunteer were acquired.ROI were drawn manually based on the transverse CT images and transferred to the corresponding PET slices.Radiation-absorbed doses were calculated using the medical internal radiation dosimetry (MIRD) method.Results The highest concentrations of 13 N-ammonia were found in the heart,liver and kidneys,followed by pancreas,brain,spleen and stomach.The organ of highest absorbed dose was heart with (7.14±3.63) × 10-3 mGy/MBq.The whole-body absorbed dose was (2.11±0.44) × 10 3 mGy/MBq.The whole-body effective dose was (6.58± 1.23) × 10-3 mSv/MBq.Conclusion As one of the most important myocardial perfusion tracers,the whole-body 13 N-NH3 · H2 O PET appears to be safe for humans.

Objective To investigate the expression of glutamine synthetase ( GS ) in prostate cancer and the utility of 13 N?NH3 PET/CT in detecting prostate cancer. Methods The uptake ratio of 13 N?NH3 and the expression of GS in PC3 and DU145 cells were measured by Western blot and PCR methods. A total of 34 patients with suspected prostate cancer underwent 13 N?NH3 PET/CT imaging and prostate biopsy. Immunohistochemistry staining of GS was performed and Gleason scores of tumors were evaluated. One?way analysis of variance, the least significant difference?t test and Spearman correlation analysis were used to an?alyze data. Results The uptake of 13 N?ammonia in PC3 and DU145 cells elevated along with the decrease of glutamine in medium. The expression of GS mRNA and protein also increased when glutamine was de?creased. In biopsy samples, the mean GS expression scores of prostate cancer, benign prostatic hyperplasia (BPH) and prostatitis were 7.76±2.57, 3.98±2.60, 3.34±0.36, respectively (F=36.85, t1=7.97, t2=4?45, all P<0.05), which had a weak correlation with Gleason scores (rs=0.52, P<0.05). In 34 patients, the mean SUVmax of prostate cancer segments (1.56±0.58 and 1.14±0.22;F=5.966, t1=2.63, t2=2.65, all P<0.05). There was a weak correlation between GS expression scores and the uptake of 13 N?ammonia in prostate cancer (rs=0.47, P<0.05). Conclusions Up?regulated expression of GS is common in prostate cancer cells. GS is the main reason for the uptake of 13 N?ammonia, which is a useful tracer for prostate cancer imaging.

Objective To investigate the diagnostic efficacy of 13N-NH3 and 18F-FDG PET/CT in the evaluation of untreated gliomas.Methods A total of 45 consecutive patients (29 males,16 females;age range 14-75 years,average age (47.47± 15.64) years) with final diagnosis of glioma from August 2009 to May 2012 were retrospectively analyzed.PET/CT imaging was performed with both 18F-FDG and 13N-NH3.Imaging results were analyzed by tumor-to-gray matter (T/G) ratios.ROC curve analysis was conducted to determine the optimal T/G cutoff values between low-grade and high-grade gliomas.One-way analysis of variance was applied to assess the differential efficacy of the two tracers in different grade of glioma.Results Forty-eight separate lesions were identified (WHO grade Ⅱ,n=16;grade Ⅲ,n=12;and grade Ⅳ,n=20).The sensitivities of 13N-NH3 PET/CT and 18F-FDG PET/CT on predicting high-grade gliomas were 91％(29/32) and 66％ (21/32),respectively.The optimal T/G cutoff values for 18F-FDG and 13N-NH3 were 0.64 and 0.86 with the AUC of 0.910 and 0.943,respectively.The sensitivity and positive predictive value of predicting high-grade gliomas with optimal cutoff values were 84％ (27/32) and 93％ (27/29)for 18F-FDG PET/CT,those for 13N-NH3 PET/CT were 94％ (30/32) and 94％ (30/32),respectively.Conclusion 13N-NH3 PET/CT is superior to 18F-FDG PET/CT not only in separating low-grade gliomas from high-grade ones,but also in the detection of high-grade gliomas for better tumor to normal gray matter contrast.