Objectives: Respiratory motion degrades the quantitative accuracy and test-retest (TRT) reliability of fluorine-18 fluorodeoxyglucose ([18F] FDG) positron emission tomography (PET)/computed tomography (CT) in lung cancer. This study investigated whether a deep-learning-based respiratory motion correction (RMC) method improves the TRT reliability and image quality of [18F] FDG PET tumor quantification compared with non-motion-corrected (NMC) reconstructions. Methods: Thirty-one patients with primary lung cancer underwent three PET acquisitions: whole body free breathing (Scan1), thoracic free breathing (Scan2), and thoracic controlled breathing (ScanCB). Each dataset was reconstructed with and without RMC. Visual assessments of liver motion artifacts, lesion clarity, and PET-CT co-registration were scored. Lung tumors were segmented to derive standardized uptake value max (SUVmax), SUVmean, metabolic tumor volume (MTV), PET-derived lesion length (PLL), and total lesion glycolysis (TLG). Visual image scores and TRT reliability of tumor quantification were compared using Kruskal-Wallis one-way analysis of variance and intraclass correlation coefficients (ICCs). Results: RMC reconstructions achieved higher visual scores of lesion clarity and PET-CT co-registration across all lung lobes and significantly reduced liver motion artifacts compared with NMC reconstructions. Differences in SUVmax, SUVmean, PLL, MTV, and TLG between Scan2 and ScanCB were significantly smaller with RMC than with NMC. ICCs for SUVmax, SUVmean, MTV, and TLG were higher between scans with RMC than NMC reconstructions, indicating improved TRT reliability. Conclusions: The deep-learning-based RMC method improved the image quality and TRT reproducibility of [18F] FDG PET/CT quantification in lung cancer, supporting its potential for routine adoption in therapy-response assessments.

[18F]Florbetazine ([18F]FBZ) is a novel Aβ tracer with imaging characteristics similar to [11C]PiB. This study aimed to establish Centiloid conversion equations for [18F]FBZ and to evaluate its quantification precision relative to [11C]PiB across different image-processing pipelines and effective image resolutions (EIRs). Methods: Paired [11C]PiB and [18F]FBZ PET scans were acquired in 53 participants. Centiloid conversion equations for [18F]FBZ standardized uptake value ratio (SUVR), derived from both the standard SPM pipeline and a FreeSurfer pipeline, were calculated following the Level-2 analysis proposed by Klunk et al. The variance ratio of Centiloids derived from [18F]FBZ SUVR to those derived from standard [11C]PiB SUVR in YCs was computed to compare quantification precision. Additionally, the linear relationships between [18F]FBZ and [11C]PiB SUVR were evaluated under different EIRs. Results: The Centiloid conversion equation for [18F]FBZ SUVR using the standard SPM pipeline was: Centiloid=98.6 × [18F]FBZ SUVRstd–99.8 (variance ratio=0.92). For the FreeSurfer pipeline, the conversion was: Centiloid=110.1 × [18F]FBZ SUVRfs–108.1 (variance ratio=0.55). Robust linear correlations between [11C]PiB and [18F]FBZ SUVR were observed across EIRs with the SPM pipeline, whereas regression parameters varied across EIRs with the FreeSurfer pipeline. Conclusion: [18F]Florbetazine SUVR can be reliably converted to Centiloid units. Compared with [11C]PiB, [18F]FBZ demonstrated equal or improved quantification precision, supporting its broader use in clinical and research Aβ imaging.

This study aims to compare [18F]Florbetazine (FBZ, [18F]92) with [11C]Pittsburgh compound B (PiB) and [18F]Florbetapir (FBP) PET imaging to evaluate the diagnostic efficacy of FBZ and explore differences in topographical deposition patterns between FBZ and PiB/FBP. Seventy-eight participants were included, with 40 in the FBZ-PiB subgroup (9 healthy controls [HCs], 9 with non-AD dementia, and 22 with AD) and 38 in the FBZ-FBP subgroup (10 HCs, 9 with non-AD dementia, 1 with mild cognitive impairment [MCI], and 18 with AD). All images were visually evaluated by two trained nuclear medicine physicians and quantitatively analyzed using global and regional standardized uptake value ratio (SUVr). Visual interpretation of FBZ scans achieved a diagnostic sensitivity of 100 https://clinicaltrials.gov/search?term=NCT06141356 .

OBJECTIVE:Obesity is a global health issue that causes altered gut microbiota and a wide variety of diseases, such as osteoporosis. The association between altered gut microbiota metabolites and high-fat diet (HFD)-induced osteoporosis has not been thoroughly investigated. 3-Indolepropionic acid (IPA) is a gut microbiota metabolite that is deficient in obese mice. The purpose of this study is to examine wheter IPA affects osteoporosis in HFD-induced obese mice. MATERIALS AND METHODS:Mice were fed with HFD for 12 weeks, during which IPA or vancomycin was administered. Micro-computed tomography, hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining were used to evaluate osteoporosis and osteoclast activation in vivo. Cultured bone marrow macrophages were used to examine osteoclast activation in vitro. Western blot, immunohistochemical staining, and immunofluorescence staining were used to investigate the nuclear factor kappa B (NF-κB) and NLRP3 signaling pathways. RESULTS:Reduced bone mass and noticeable osteoclast activation were observed in mice fed with HFD and vancomycin. IPA supplementation alleviated systemic inflammatory response, inhibited osteoclast activation, and improved bone mass in mice. Mechanistically, IPA inhibited the phosphorylation of NF-κB, thus, reducing the expression levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and inhibiting osteoclast activation. CONCLUSION:These findings suggest that IPA-induced inhibition of osteoclast activation in the HFD environment was mediated via the NF-κB/NLRP3 pathway. Our study suggests that IPA consumption may help manage obesity-induced osteoporosis.

Vitronectin, a protein derived the human placenta, has been identified as an inducer of insulin resistance in trophoblast cells in gestational diabetes mellitus (GDM). As a secreted protein, vitronectin may have systemic effects on dysregulated glucose metabolism in GDM. To address this speculation, we generated a GDM mouse model using high-fat diet-induced obese mice. Consistent with findings in placentas of GDM patients, GDM mouse placentas showed higher vitronectin expression, accompanied by increased serum vitronectin levels. Reduced insulin signaling transduction was observed in both the placentas and livers of GDM mice, along with enhanced hepatic gluconeogenesis. To further explore the role of vitronectin in hepatic gluconeogenesis, we constructed an adeno-associated virus expressing Vtn (AAV-VTN), which was administered to mice via tail vein injection. In AAV-VTN-treated mice, glucose production from exogenous pyruvate increased, and the expression of gluconeogenic genes in the liver was upregulated, indicating that hepatic gluconeogenesis was stimulated by vitronectin. Mechanistically, vitronectin binds to its receptor CD51/61, activating the cAMP/PKA/CREB axis in hepatocytes, thereby promoting hepatic gluconeogenesis. In summary, our findings suggest that placenta-derived vitronectin plays a critical role in inducing insulin resistance in the liver in GDM. Moreover, vitronectin stimulates hepatic gluconeogenesis through activation of the cAMP/PKA/CREB axis. These results point to vitronectin as a potential therapeutic target for managing hyperglycemia in GDM.

A deep progressive learning method for PET image reconstruction named deep progressive reconstruction (DPR) method was developed and presented in previous works. It has been shown in previous study that the DPR with one-third duration can maintain the image quality as OSEM with standard dose (3.7 MBq/kg). Subsequent studies have shown we can reduce the administered activity of 18F-FDG by up to 2/3 in a real-world deployment with DPR. The aim of this study is to assess the impact of the use of DPR on Deauville score (DS) and clinical interpretation of PET/CT in patients with lymphoma. A total of 87 lymphoma patients (age, 45.1 ± 14.9 years) who underwent 18F-FDG PET imaging for during or post-treatment follow-up from November 2020 to February 2024 were prospectively enrolled. The patients were randomly assigned to two groups, including the 1/3 standard dose group and the standard dose group. Forty-four patients were injected with 1/3 standard dose (1.23 MBq/kg) and scanned for 6 min per bed and were reconstructed: ordered-subsets expectation maximization (OSEM) with 6 min per bed (OSEM_6 min_1/3), OSEM_2 min_1/3 and DPR_2 min_1/3. Forty-three patients were scanned according to the standard protocol (3.7 MBq/kg) and were reconstructed: OSEM with 2 min per bed (OSEM_2 min_full), OSEM_40 s_full and DPR_40 s_full. Additionally, the conventional 5-point scale measurement analysis was performed and DS for lymphoma were determined in different groups. Wilcoxon signed-rank test was used to compare the mean values of liver SUVmax and mediastinal blood pool (MBP) SUVmax in each group. Likert scale and DS were evaluated using Wilcoxon signed rank test. The patients with OSEM_6 min_1/3 and DPR_2 min_1/3 showed good image quality with 5(5,5) and 5(4,5) of Likert scoring, as well as the patients with OSEM_2 min_full and DPR_40 s_full. No significant difference was found between the OSEM_6 min_1/3 and DPR_2 min_1/3 groups in terms of liver SUVmax and MBP SUVmax (P = 0.452 and 0.430), as well as the patients with OSEM_2 min_full and DPR_40 s_full (P = 0.105 and 0.638). No significant difference was found between the OSEM_6 min_1/3 and DPR_2 min_1/3 groups in terms of lesion SUVmax (P = 0.080). There was a significant differences in lesion SUVmax between OSEM-2 min_full with DPR-40 s_full (P = 0.027). The DS results were consistent (100

Objectives To investigate PET/CT registration and quantification accuracy of thoracic lesions of a single 30-second deep-inspiration breath-hold (DIBH) technique with a total-body PET (TB-PET) scanner, and compared with free-breathing (FB) PET/CT. Methods 137 of the 145 prospectively enrolled patients finished a routine FB-300 s PET/CT exam and a 30-second DIBH TB-PET with chest to pelvis low dose CT. The total-body FB-300 s, FB-30 s, and DIBH-30 s PET images were reconstructed. Quantitative assessment (SUVmax and SUVmean of lung and other organs), PET/CT registration assessment and lesion analysis (SUVmax, SUVpeak, SUVmean and tumor-background ratio) were compared with Wilcoxon signed-rank tests. Results The SUVmax and SUVmean of the lung with DIBH-30 s were significantly lower than those with FB. The distances of the liver dome between PET and CT were significantly smaller with DIBH-30 s than with FB. 195 assessable lesions in 106 patients were included, and the detection sensitivity was 97.9 % and 99.0 % in FB-300 s, and DIBH-30 s, respectively. For both small co-identified lesions (n = 86) and larger co-identified lesions with a diameter ≥ 1 cm (n = 91), the lesion SUVs were significantly greater with DIBH-30 s than with FB-300 s. Regarding lesion location, the differences of the SUVs for the lesions in the lower thorax area (n = 97, p < 0.001) were significant between DIBH-30 s and FB-300 s, while these differences were not statistically significant in the upper thorax (n = 80, p > 0.05). The lesion tumor-to-surrounding-background ratio (TsBR) was significantly increased, both in the upper and lower thorax. Conclusion The TB DIBH PET/CT technique is feasible in clinical practice. It reduces the background lung uptake and achieves better registration and lesion quantification, especially in the lower thorax.

Nowadays, total body PET has already entered the medical centers and enabled various clinical applications due to its superior imaging capabilities, especially the high sensitivity. However, the potential of the total body PET in the clinical evaluation of radiopharmaceuticals remains underexplored. The development and regulatory processes for radiopharmaceuticals present unique challenges that total body PET could address. In the safety evaluation of radiopharmaceuticals, the internal radiation dosimetry demands images with high quality and quantitative accuracy, which can be achieved using the total body PET. The current clinical pharmacokinetic study for radiopharmaceuticals still relies on invasively sampling of blood and other body fluid, causing discomfort of participant and difficulty in implementation. With the total body PET, the radioactive concentration of the drug in various blood vessels can be assessed noninvasively, facilitating the pharmacokinetic study. The parametric analysis over the total body based on compartment models also sheds light on the pharmacokinetics of the radiopharmaceutical. A special requirement for multi-center clinical research involving PET and SPECT is the harmonization of the quantitative performance among different imaging equipment, and the discrepancy between the total body PET and short axial field of view PET scanners may add to the complexity. To date, there are several successful examples of clinical trials of innovative radiopharmaceuticals using the total body PET, involving different types of tracers ranging from small molecules, peptides, nanobodies, minibodies, and aptamers. In conclusion, total body PET has the potential to revolutionize the clinical evaluation of radiopharmaceuticals and will play a crucial role in future drug development.

Total-body PET, an emerging technique, enables high-quality simultaneous total-body dynamic PET acquisition and accurate kinetic analysis. It has the potential to facilitate the study of multiple tracers while minimizing radiation dose and improving tracer-specific imaging. This advancement holds promise for enhancing the development and clinical evaluation of drugs, particularly radiopharmaceuticals. Multiple clinical trials are using a total-body PET scanner to explore existing and innovative radiopharmaceuticals. However, challenges persist, along with the opportunities, with regard to the use of total-body PET in drug development and evaluation. Specifically, considerations relate to the role of total-body PET in clinical pharmacologic evaluations and its integration into the theranostic paradigm. In this review, state-of-the-art total-body PET and its potential roles in pharmaceutical research are explored.

[18F]-Florbetazine 18 F]-Florbetazine ([18F]-92) 18 F]-92) is a selective PET tracer for (3-amyloid (A(3) depositions with a novel diaryl-azine scaffold to reduce lipophilicity and to achieve higher gray-to-white matter contrast. We aimed to assess its diagnostic value in Alzheimer's disease (AD) and pharmacokinetics characteristics in human subjects. Methods: Six healthy controls (HCs) and nine AD patients underwent dynamic PET examination with [18F]- 18 F]- Florbetazine and a structural MRI scan. The time-activity-curves (TACs) for volumes of interest (VOIs) in cerebral cortex, cerebellar cortex and cerebral white matter was depicted and their standardized uptake value ratios (SUVRs) with cerebellar cortex as reference were compared between HCs and AD patients. The cerebral gray-to- white matter SUV ratio (GWR) was also calculated. Results: In HCs, radioactivities in the cerebral cortex VOIs were homogeneously low and at the same level as in cerebellar cortex, while in AD patients, cortical VOIs expected to contain A(3 exhibited high radioactivity. Cerebral cortex SUVRs remain relatively low in HCs while keep increasing along with time in AD patients. After 15 min, the cerebral cortex SUVRs became significant higher in AD patients compared to HCs with 100 % discrimination accuracy. In AD patients, GWR remained over 1.3 for all time intervals and visual inspection showed lower uptake in cerebral white matter compared to cerebral cortex. Conclusion: [18F]-Florbetazine 18 F]-Florbetazine PET showed high uptake on A(3 plaques and high gray-to-white contrast in AD patients that are favorable in visual read. [18F]-Florbetazine 18 F]-Florbetazine can be potentially used for detection and quantification of A(3 depositions in the living human brain.

[18F]-Florbetazine ([18F]-92) is a selective PET tracer for β-amyloid (Aβ) depositions with a novel diaryl-azine scaffold to reduce lipophilicity and to achieve higher gray-to-white matter contrast. We aimed to assess its diagnostic value in Alzheimer's disease (AD) and pharmacokinetics characteristics in human subjects. Methods Six healthy controls (HCs) and nine AD patients underwent dynamic PET examination with [18F]-Florbetazine and a structural MRI scan. The time-activity-curves (TACs) for volumes of interest (VOIs) in cerebral cortex, cerebellar cortex and cerebral white matter was depicted and their standardized uptake value ratios (SUVRs) with cerebellar cortex as reference were compared between HCs and AD patients. The cerebral gray-to-white matter SUV ratio (GWR) was also calculated. Results In HCs, radioactivities in the cerebral cortex VOIs were homogeneously low and at the same level as in cerebellar cortex, while in AD patients, cortical VOIs expected to contain Aβ exhibited high radioactivity. Cerebral cortex SUVRs remain relatively low in HCs while keep increasing along with time in AD patients. After 15 min, the cerebral cortex SUVRs became significant higher in AD patients compared to HCs with 100 % discrimination accuracy. In AD patients, GWR remained over 1.3 for all time intervals and visual inspection showed lower uptake in cerebral white matter compared to cerebral cortex. Conclusion [18F]-Florbetazine PET showed high uptake on Aβ plaques and high gray-to-white contrast in AD patients that are favorable in visual read. [18F]-Florbetazine can be potentially used for detection and quantification of Aβ depositions in the living human brain.

Background: Patients with lymphoma receive multiple positron emission tomography/computed tomography (PET/CT) exams for monitoring of the therapeutic response. With PET imaging, a reduced level of injected fluorine-18 fluorodeoxyglucose ([F-18]FDG) activity can be administered while maintaining the image quality. In this study, we investigated the efficacy of applying a deep learning (DL) denoising-technique on image quality and the quantification of metabolic parameters and Deauville score (DS) of a low [F-18]FDG dose PET in patients with lymphoma. Methods: This study retrospectively enrolled 62 patients who underwent [F-18]FDG PET scans. The low-dose (LD) data were simulated by taking a 50% duration of routine-dose (RD) PET list-mode data in the reconstruction, and a U-Net-based denoising neural network was applied to improve the images of LD PET. The visual image quality score (1 = undiagnostic, 5 = excellent) and DS were assessed in all patients by nuclear radiologists. The maximum, mean, and standard deviation (SD) of the standardized uptake value (SUV) in the liver and mediastinum were measured. In addition, lesions in some patients were segmented using a fixed threshold of 2.5, and their SUV, metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG) were measured. The correlation coefficient and limits of agreement between the RD and LD group were analyzed. Results: The visual image quality of the LD group was improved compared with the RD group. The DS was similar between the RD and LD group, and the negative (DS 1-3) and positive (DS 4-5) results remained unchanged. The correlation coefficients of SUV in the liver, mediastinum, and lesions were all >0.85. The mean differences of SUVmax and SUVmean between the RD and LD groups, respectively, were 0.22 [95% confidence interval (CI): -0.19 to 0.64] and 0.02 (95% CI: -0.17 to 0.20) in the liver, 0.13 (95% CI: -0.17 to 0.42) and 0.02 (95% CI: -0.12 to 0.16) in the mediastinum, and -0.75 (95% CI: -3.42 to 1.91), and -0.13 (95% CI: -0.57 to 0.31) in lesions. The mean differences in MTV and TLG were 0.85 (95% CI: -2.27 to 3.98) and 4.06 (95% CI: -20.53 to 28.64) between the RD and LD groups. Conclusions: The DL denoising technique enables accurate tumor assessment and quantification with LD [F-18]FDG PET imaging in patients with lymphoma.

Inflammation is a common feature both for Parkinson’s disease (PD) and obesity-associated metabolic syndromes. Inflammation mediated by inflamed macrophages in white adipose tissue plays a pivotal role for the pathogenesis of metabolic syndromes. Exosomes are important carriers connecting peripheral tissues and the central nervous system (CNS). Therefore, we speculate that exosomes derived from inflamed macrophages may be involved in the pathological progression of PD. Here, we prepared exosomes from lipopolysaccharide (LPS) or interferon gamma (IFNγ) treated macrophages (inflamed macrophages) and examined their potential roles in PD. Our data showed that exosomes from inflamed macrophages stimulate proinflammatory cytokine expression in primary microglia and astrocytes. In vivo, inflamed macrophage exosomes induce behavioral defects in mice as evidenced by shortened duration in the rotarod test and prolonged latency in the pole test. The treatment of exosomes also reduces tyrosine hydroxylase (TH) positive cells in the substantia nigra pars compacta (SNpc) and striatum. All these PD-like phenotypes are likely due to the activation of microglia and astrocytes induced by exosomes from inflamed macrophages. Exosome sequencing, together with bioinformatics analysis and functional studies, revealed that exosomal miRNAs such as miR-155-5p are likely a key factor for inducing an inflammatory response in glial cells. These results indicate that exosomes derived from inflamed macrophages are likely a causative factor for developing PD. In this regard, inflamed macrophage exosomes might be a linker transducing the peripheral tissue inflammation into the CNS.

目的:探讨长链非编码RNA(lncRNA)VIM反义RNA 1(VIM-AS1)在糖尿病视网膜病变中的潜在分子机制.方法:使用qRT-PCR测定LncRNA VIM-AS1、miR-497-5p和FBXW7 mRNA的表达.使用蛋白质印迹检测FBXW7蛋白水平.分别使用CCK-8实验、伤口愈合实验和流式细胞技术分析评估细胞增殖、迁移和凋亡.通过双荧光素酶报告基因分析验证lncRNA VIM-AS1、miR-497-5p和FBXW7之间的结合关系.结果:在高糖处理的ARPE-19细胞中,LncRNAVIM-AS1和FBXW7的表达显著降低,而miR-497-5p的表达上调.LncRNA VIM-AS1可以通过竞争性结合miR-497-5p上调FBXW7的表达.LncRNA VIM-AS1过表达能够促进HG处理的ARPE-19细胞的增殖和迁移,并抑制细胞凋亡,而miR-497-5p过表达消除了 lncRNA VIM-AS1过表达对HG处理的ARPE-19细胞的影响.此外,FBXW7敲低消除了 miR-497-5p对HG处理的ARPE-19细胞表型的抑制.结论:lncRNA VIM-AS 1可通过调控miR-497-5p/FBXW7轴促进HG处理的ARPE-19细胞增殖和迁移,同时抑制细胞凋亡,提示lncRNA VIM-AS1作为治疗靶点潜力巨大.

目的 探讨分析临床路径教学法(clinical path teaching method,CPTM)及以问题为基础的学习法(problem based learning,PBL)两种教学法联合应用于内分泌科的临床实习教学中的效果.方法 选取2020年1月—2022年1月在扬州大学附属第五临床医学院内分泌科临床实习的60名医学生作为研究对象,将其随机分为对照组(n=30)与研究组(n=30).以2型糖尿病为教学案例,对照组采用传统教学模式,研究组采用CPTM联合PBL的教学模式,评估两组临床实习医学生在实习期间的教学效果.结果 研究组的理论成绩、实践考核成绩、主观能力提升评测及教学模式满意度均高于对照组,差异有统计学意义(P<0.05).结论 CPTM教学贴近临床,PBL利于自主学习,两种教学模式的融合能有效训练学生发现问题和解决问题的能力,更有利于学生理解内分泌基础理论知识并将其应用于临床.