Improvement of phoswich detector-based ß+/γ-ray discrimination algorithm with deep learning.

BACKGROUND: Positron probes can accurately localize malignant tumors by directly detecting positrons emitted from positron-emitting radiopharmaceuticals that accumulate in malignant tumors. In the conventional method for direct positron detection, multilayer scintillator detection and pulse shape discrimination techniques are used. However, some γ-rays cannot be distinguished by conventional methods. Accordingly, these γ-rays are misidentified as positrons, which may increase the error rate of positron detection. PURPOSE: To analyze the energy distribution in each scintillator of the multilayer scintillator detector to distinguish true positrons and γ-rays and to improve the positron detection algorithm by discriminating true and false positrons. METHODS: We used Autoencoder, an unsupervised deep learning architecture, to obtain the energy distribution data in each scintillator of the multilayer scintillator detector. The Autoencoder was trained to separate the combined signals generated from the multilayer scintillator detector into two signals of each scintillator. An energy window was then applied to the energy distribution obtained using the trained Autoencoder to distinguish true positrons from false positrons. Finally, the performance of the proposed method and conventional positron detection algorithm was evaluated in terms of the sensitivity and error rate for positron detection. RESULTS: The energy distribution map obtained using the trained Autoencoder was proven to be similar to that of the simulated results. Furthermore, the proposed method demonstrated a 29.79% (+0.42%p) increase in positron detection sensitivity compared to the conventional method, both having an equal error rate of 0.48%. However, when both methods were set to have the same sensitivity of 1.83%, the proposed method had an error rate that was 25.0% (-0.16%p) lower than that of the conventional method. CONCLUSIONS: We proposed and developed an Autoencoder-based positron detection algorithm that can discriminate between true and false positrons with a smaller error rate than conventional methods. We verified that the proposed method could increase the positron detection sensitivity while maintaining a low error rate compared to the conventional method. If the proposed algorithm is implemented in handheld positron detection probes or cameras, diseases such as cancers can be more accurately localized in a shorter time compared with using traditional methods.

Inhibition of LFA-1/ICAM-1-mediated cell adhesion by stilbene derivatives from Rheum undulatum.

Six stilbenes were isolated from the methanol extract of Rheum undulatum rhizomes by bioactivity-guided fractionation. The structures of the compounds were determined by spectroscopic analysis ((1)H-, (13)C-NMR and MS), to be desoxyrhapontigenin (1), rhapontigenin (2), trans-resveratrol (3), piceatannol (4), piceatannol-3'-O-ß-D-glucopyranoside (5) and isorhapontin (6). Compounds 1-4 inhibited the direct binding between sICAM-1 and LFA-1 of the THP-1 cells in a dose-dependent manner with IC(50) values of 50.1, 25.4, 33.4 and 45.9 µM, respectively. On the other hand, the other compounds 5 and 6 with a glucose moiety in each molecule did not show any inhibitory activity in the cell adhesion assay (IC(50) values of >100.0 µM). Compounds 2, 3 and 4 also had an inhibitory effect on direct binding between sVCAM-1 and VLA-4 of THP-1 cells. This suggests that the stilbenes from Rheum undulatum rhizomes are good candidates for therapeutic strategies towards inflammation.

Increased oxidative stress in the airway and development of allergic inflammation in a mouse model of asthma.

BACKGROUND: The exact pathogenic role of oxidative stress in the development of allergic airway inflammation is still largely unknown. OBJECTIVE: To investigate a possible link between increased pulmonary oxidative stress and the pivotal features of asthma during the mounting of an allergic inflammatory response. METHODS: To determine the relationship between oxidative stress and allergic inflammatory responses, we evaluated the sequential kinetics of oxidative stress in the lung, the development of airway inflammation, mucin hypersecretion, and airway hyperresponsiveness (AHR) in an ovalbumin (OVA)-sensitized and challenged mouse with and without antioxidant. Parameters were measured at 9 points for more than 28 days, starting from the first day of OVA challenge with or without antioxidant treatment. The ratio of reduced to oxidized glutathione in the lungs and levels of intracellular reactive oxygen species (ROS) in the bronchial epithelium were serially measured. Bronchoalveolar lavage fluid cells, histopathologic features, and AHR were analyzed at the same time points. RESULTS: The reduced to oxidized glutathione ratio was reduced from immediately after OVA challenge to day 1, remained at this level until day 1, and rapidly recovered to the normal level after more than 2 days. Intracellular ROS levels in the bronchial epithelium followed similar kinetics. The inflammatory cells in bronchoalveolar lavage fluid reached a maximum of 3 days and decreased progressively thereafter. Histopathologic examination revealed that substantial airway inflammation persisted through day 28. The proportion of mucin-producing epithelial cells significantly increased after day 1, reached a maximum at day 3, and remained at this level until day 5. The AHR peaked on day 1 and normalized within 5 days. The pretreatment of antioxidant significantly reduced not only the increased ROS levels but also development of other phenotypes of asthma. CONCLUSION: These results indicate that increased oxidative stress in the lung precedes other pivotal phenotypes of allergic airway disease, suggesting a critical role for increased oxidative stress in the induction of allergic airway inflammation.

Chlamydophila pneumoniae triggers release of CCL20 and vascular endothelial growth factor from human bronchial epithelial cells through enhanced intracellular oxidative stress and MAPK activation.

BACKGROUND: Chlamydophila pneumoniae may contribute to the pathogenesis of asthmatic airway inflammation through chemical mediators secreted by C. pneumoniae-infected bronchial epithelial cells (BECs). Recently, CCL20 and vascular endothelial growth factor (VEGF) were reported to be released from BECs and to play a role in the pathogenesis of asthma. OBJECTIVE AND METHODS: To determine if C. pneumoniae infection of BECs induces the secretion of CCL20 and VEGF, we measured that by ELISA in human BECs infected with C. pneumoniae. Transcripts of CCL20 and VEGF were assayed by semi-quantitative RT-PCR. To investigate the underlying mechanism, the activation of MAPK and intracellular reactive oxygen species (ROS) in these C. pneumoniae-infected BECs was measured, as well as the effects of inhibitors of MAPK and ROS on CCL20 and VEGF expression. RESULTS: Compared with non-infected BECs, C. pneumoniae-infected BECs showed enhanced secretion of CCL20 and VEGF. C. pneumoniae-infected BECs also showed enhanced intracellular ROS and an increased ratio of phosphorylated to non-phosphorylated p38. Inhibition of p38 suppressed CCL20 and VEGF secretion, as did a NADPH oxidase blocker and an antioxidant, in C. pneumoniae-infected BECs. CONCLUSION: C. pneumoniae infection of BECs may play a role in the pathogenesis of asthma through the enhanced production of CCL20 and VEGF. The association between increased cytokine production and increased intracellular ROS suggests that antioxidants may benefit asthmatics in selected situations.

Allergen-induced CD11b+ CD11c(int) CCR3+ macrophages in the lung promote eosinophilic airway inflammation in a mouse asthma model.

Although the recruitment of macrophages to the lung is a central feature of airway inflammation, its function in ongoing T(h)2 cell-mediated eosinophilic airway inflammation remains controversial. Here, we have demonstrated that the allergen-induced CD11b(+) CD11c(int) macrophage expressing CC chemokine receptor 3 (CCR3) in the lung performs a crucial function in the induction of eosinophilic asthma in a murine model. In the lungs of normal mice, residential cells evidencing high granularity phenotypically evidenced CD11b(int) CD11c(+) or CD11b(+) CD11c(int) cells, appearing at a 2:1 ratio. After allergen challenge, however, this reverses dramatically, up to a ratio of one to six. Approximately 91% of increased CD11b(+) CD11c(int) cells evidenced the expression of the CCR3 eotaxin receptor, but not other chemokine receptors, such as CCR5 and CXCR4. Interestingly, the CD11b(+) CD11c(int) cells purified from the lungs of OVA (ovalbumin)-sensitized and challenged mice evidenced higher antigen-presenting activity than was observed in CD11b(int) CD11c(+) cells. In order to investigate the in vivo function of CD11b(+) CD11c(int) cells, the cells were isolated from the lungs of OVA-sensitized and challenged mice and then adoptively transferred prior to the allergen challenge of normal mice. In the CD11b(+) CD11c(int)-transferred mice airway hyperresponsiveness, eosinophilic inflammation in the lung and T(h)2 cytokine secretion in the bronchoalveolar lavage fluids were significantly enhanced as the result of OVA challenge, as compared with the mice that received OVA-primed CD90(+) T cells or CD11b(int) CD11c(+) cells. These findings show that CD11b(+) CD11c(int) macrophages expressing CCR3 as key pro-inflammatory cells are both necessary and sufficient for allergen-specific T cell stimulation during ongoing eosinophilic airway inflammation.