Objective:To assess the β-amyloid (Aβ) deposition of voxel-based PET imaging in Alzheimer′s disease (AD) and its relationships with blood biomarkers (Aβ).Methods:From January 2015 to December 2018, a total of 23 AD patients (9 males, 14 females, age (68.5±9.0) years; duration: (40.9±23.3) months; 8 mild patients, 15 moderate or severe patients) who underwent Aβ PET and with positive imaging results in Daping Hospital, Army Medical University were retrospectively enrolled. The information of Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) were collected. Blood level of Aβ42, Aβ40 were measured. Differences of those metrics including Aβ42/Aβ40 between mild and moderate or severe patients were compared. For all 11C-Pittsburgh compound B (PIB) PET images, voxel-based one-sample independent t test analyses were performed. Voxel-based two-sample independent t test analyses were also performed between mild and moderate or severe patients. The voxel-based Pearson correlation analyses were run to assess the associations between blood metrics and Aβ deposition of 11C-PIB PET. Results:Comparing with mild patients, moderate or severe patients had lower MMSE (9.67±4.37 vs 17.13±2.80; t=4.349, P<0.001) and longer duration ((48.8±23.8) vs (26.0±13.5) months; t=-2.489, P<0.05). On voxel-wise analysis, amyloid PET illustrated brain Aβ deposition in bilateral frontal, right temporal, right occipital and posterior cingulate regions ( t values: 0.44-0.67, all P<0.001). Within AD, Aβ42/Aβ40 ( r values: from -0.62 to -0.41, 0.41-0.66, all P<0.05) were associated with amyloid PET, but not associated with Aβ42 ( r values: from -0.33 to 0, all P>0.05) or Aβ40 ( r values: from -0.41 to 0, all P>0.05). Conclusions:Based on voxel-wise analysis, 11C-PIB PET has comparable value for brain Aβ deposition. Aβ42/Aβ40 has the potential to predict brain Aβ deposition.

Purpose To explore the application value of combining 18F-FDG PET images with interpretable deep learning radiomics(IDLR)models in the differential diagnosis of primary Parkinson's disease(IPD)and atypical Parkinson's syndrome.Materials and Methods This cross-sectional study was conducted using the Parkinson's Disease PET Imaging Benchmark Database from Huashan Hospital,Fudan University from March 2015 to February 2023.A total of 330 Parkinson's disease patients underwent 18F-FDG PET imaging,both 18F-FDG PET imaging and clinical scale information were collected for all subjects.The study included two cohorts,a training group(n=270)and a testing group(n=60),with a total of 211 cases in the IPD group,59 cases in the progressive supranuclear palsy(PSP)group,and a group of 60 patients with multiple system atrophy(MSA).The clinical information between different groups were compared.An IDLR model was developed to extract feature indicators.Under the supervision of radiomics features,IDLR features were selected from the features collected by neural network extractors,and a binary support vector machine model was constructed for the selected features in images of in testing group.The constructed IDLR model,traditional radiomics model and standard uptake ratio model were separately used to calculate the performance metrics and area under curve values of deep learning models for pairwise classification between IPD/PSP/MSA groups.The study conducted independent classification and testing in two cohorts using 100 10-fold cross-validation tests.Brain-related regions of interest were displayed through feature mapping,using gradient weighted class activation maps to highlight and visualize the most relevant information in the brain.The output heatmaps of different disease groups were examined and compared with clinical diagnostic locations.Results The IDLR model showed promising results for differentiating between Parkinson's syndrome patients.It achieved the best classification performance and had the highest area under the curve values compared to other comparative models such as the standard uptake ratio model(Z=1.22-3.23,all P<0.05),and radiomics model(Z=1.31-2.96,all P<0.05).The area under the curve values for the IDLR model in differentiating MSA and IPD were 0.935 7,for MSA and PSP were 0.975 4,for IPD and PSP were 0.982 5 in the test set.The IDLR model also showed consistency between its filtered feature maps and the visualization of gradient-weighted class activation mapping slice thermal maps in the radiomics regions of interest.Conclusion The IDLR model has the potential for differential diagnosis between IPD and atypical Parkinson's syndrome in 18F-FDG PET images.

Objective:To compare the effects of different reference brain regions on the semi-quantitative SUV ratio (SUVR) of 18F-Florzolotau PET images of Alzheimer′s disease (AD). Methods:The 18F-Florzolotau PET images of 28 (13 males, 15 females, age (57.3±9.5) years) normal controls (NC), 19 patients (4 males, 15 females, age (73.3±7.3) years) with β-amyloid (Aβ)-positive mild cognitive impairment (MCI) and 40 patients (19 males, 21 females, age (61.9±9.1) years) with AD were collected from Huashan Hospital, Fudan University between November 2018 and July 2020. Six semi-quantitative reference brain regions were defined, including whole cerebellum (WC), cerebellar gray matter (GM), cerebellar white matter (WM), parametric estimation of reference signal intensity (PERSI), WC after partial volume correction (WC_pvc), cerebellar GM after partial volume correction (GM_pvc). SUVR was calculated for 14 ROIs, which included the whole brain defined by the automated anatomical labeling (AAL) template, fusiform, inferior temporal, lingual, middle temporal, occipital, parahippocampal, parietal, posterior cingulate, precuneus defined by the AAL template, and Meta ROI composed of the above brain regions, and braak_Ⅰ-Ⅱ, braak_Ⅲ-Ⅳ, braak_Ⅴ-Ⅵ defined by the Desikan Killiany template. AUC was used to evaluate the classification ability of SUVR, and the correlation between SUVR and clinical scale scores were assessed by Spearman rank correlation analysis. Results:The SUVRs of most brain regions showed a steady upward trend in the AD disease spectrum. In the classification task of NC and MCI, the overall performance of SUVR based on WC_pvc was relatively optimal (AUCs: 0.975-1.000). In the classification task of NC and AD, SUVRs of 10 ROIs based on the WC_pvc method showed the relatively best performance (AUCs: 0.976-1.000). The correlation between SUVR of fusiform based on cerebellar WM and mini-mental state examination (MMSE) score was the strongest ( rs=-0.72, P<0.001), and the SUVR of precuneus based on WC_pvc showed the strongest correlation with clinical dementia rating (CDR) score ( rs=0.78, P<0.001). Conclusion:The SUVR based on WC_pvc method performs well in classification and correlation tasks, and is recommended to be used in semi-quantification of 18F-Florzolotau PET images of AD.

Objective:To discuss the protective effect of polygonatum odoratum polysaccharide(POP)on the mice with cisplatin-induced acute kidney injury(AKI),and to clarify its possible mechanism.Methods:Forty male C57BL/6 mice were randomly divided into control group,model group,POP group,and ferroptosis inducer Erastin combined with POP(Erastin+POP)group,and there were 10 mice in each group.The mice in POP group and Erastin+POP group were given intragastric administration of POP(400 mg·kg-1),and on the 7th day,the mice in model group,POP group,and Erastin+POP group were intraperitoneally injected with cisplatin(20 mg·kg-1)to establish the AKI models,the mice in control group were injected with the same volume of normal saline,and the mice in Erastin+POP group were intraperitoneally injected with Erastin(40 mg·kg-1)one day in advance(on the 6th day of the experiment).After 9 d,the mice were killed and the serum and kidney tissue were collected,and the levels of serum creatinine(Scr)and blood urea nitrogen(BUN)and the levels of malondialdehyde(MDA)and glutathione(GSH)in kidney tissue of the mice in various groups were detected by kit;HE staining was used to observe the pathomorphology of kidney tissue of the mice in various groups;the expression levels of ferroptosis suppressor protein 1(FSP1),ferritin heavy chain 1(FTH1),and glutathione peroxidase 4(GPX4)proteins in kidney tissue of the mice in various groups were detected by immunohistochemistry;Western blotting method was used to detect the expression levels of nuclear factor-E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in kidney tissue of the mice in various groups.Results:Compared with control group,the levels of Scr and BUN of the mice in model group were significantly increased(P＜0.01),the level of MDA in kidney tissue was significantly increased(P＜0.01),and the level of GSH was significantly decreased(P＜0.01);most kidney tubules were dilated,the epithelial cells were swollen,the vacuolar degeneration and epithelial cells fell off,and the protein-like tubules could be seen in the lumen;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue were decreased significantly(P＜0.05 or P＜0.01).Compared with model group,the levels of Scr and BUN of the mice in POP group were significantly decreased(P＜0.01),the level of MDA in kidney tissue was significantly decreased(P＜0.01),and the level of GSH was significantly increased(P＜0.01);the dilatation of kidney tubular lumen,epithelial cell swelling,vacuolar degeneration,and epithelial cell exfoliation were decreased;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue of the mice in POP group were significantly increased(P＜0.05 or P＜0.01).Compared with POP group,the levels of Scr and BUN of the mice in Erastin+POP group were significantly increased(P＜0.01),the level of MDA in kidney tissue was increased(P＜0.05),and the level of GSH was significantly decreased(P＜0.01);the pathological injury of kidney tissue was aggravated obviously;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue were significantly decreased(P＜0.05 or P＜0.01).Conclusion:POP can reduce the AKI in the mice induced by cisplatin,and its mechanism may be related to the inhibitory effect of POP on the ferroptosis induced by cisplatin.

Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

BACKGROUND: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. METHODS: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. RESULTS: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. CONCLUSION Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Aged ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Arteries ; Atrophy ; Brain/metabolism* ; Cerebral Cortex/metabolism* ; Cerebrovascular Circulation ; Constriction, Pathologic/pathology* ; Female ; Humans ; Magnetic Resonance Imaging/methods* ; Male ; Middle Aged ; Positron-Emission Tomography/methods*