Anti-influenza drug screening and inhibition of apigetrin on influenza A virus replication via TLR4 and autophagy pathways.

Activation of Toll-like receptor (TLR) 4 plays important roles in the influenzaA virus (IAV) infection. To explore TLR4 inhibitors, 161 traditional Chinese medicines (TCMs) were screened. Further, we screened out Ixeris sonchifolia Hance, and its active compound, Apigetrin (apigenin-7-O-glucoside). Antiviral activity of Apigetrin was determined by plaque assay. We also further investigated the influence of Apigetrin on immune signaling pathways including TLRs, MAPK, NF-κB and autophagy pathways. The in-vitro results showed that the extract and its several ingredients could significantly inhibit IAV replication. Apigetrin significantly improved IAV-induced oxidative stress, inhibited the IAV-induced cytokine storm by suppressing the excessive activation of TLR3/4/7, JNK/p38 MAPK and NF-κB. Apigetrin decreased autophagosome accumulation and promoted degradation of IAV protein. Interestingly, Apigetrin antiviral activity was reversed by using H2O2 and the agonists of TLR4, JNK/p38, NF-κB and autophagy. Most important, the in-vitro effective concentration is higher than the reported plasma concentration. The in-vivo test showed that Apigetrin significantly increased the average survival time, reduced the lung edema and IAV replication. In conclusion, we have found that Ixeris sonchifolia Hance and its several ingredients can inhibit IAV infection, and the mechanisms of action of Apigetrin against IAV is by regulating TLR4 and autophagy signaling pathways.

Optimization-Based Image Reconstruction From Low-Count, List-Mode TOF-PET Data.

OBJECTIVE: We investigate an optimization-based approach to image reconstruction from list-mode data in digital time-of-flight (TOF) positron emission tomography (PET) imaging. METHOD: In the study, the image to be reconstructed is designed as a solution to a convex, non-smooth optimization program, and a primal-dual algorithm is developed for image reconstruction by solving the optimization program. The algorithm is first applied to list-mode TOF-PET data of a typical count level from physical phantoms and a human subject. Subsequently, we explore the algorithm's potential for image reconstruction in low-dose and/or fast TOF-PET imaging of practical interest by applying the algorithm to list-mode TOF-PET data of different, low-count levels from the same physical phantoms and human subject. RESULTS: Visual inspection and quantitative-metric analysis reveal that the optimization reconstruction approach investigated can yield images with enhanced spatial and contrast resolution, suppressed image noise, and increased axial volume coverage over the reference images obtained with a standard clinical reconstruction algorithm especially for low-dose TOF-PET data. SIGNIFICANCE: The optimization-based reconstruction approach can be exploited for yielding insights into potential quality upper bound of reconstructed images in, and design of scanning protocols of, TOF-PET imaging of practical significance.

Scatter Correction with Combined Single-Scatter Simulation and Monte Carlo Simulation Scaling Improved the Visual Artifacts and Quantification in 3-Dimensional Brain PET/CT Imaging with 15O-Gas Inhalation.

In 3-dimensional PET/CT imaging of the brain with 15O-gas inhalation, high radioactivity in the face mask creates cold artifacts and affects the quantitative accuracy when scatter is corrected by conventional methods (e.g., single-scatter simulation [SSS] with tail-fitting scaling [TFS-SSS]). Here we examined the validity of a newly developed scatter-correction method that combines SSS with a scaling factor calculated by Monte Carlo simulation (MCS-SSS). Methods: We performed phantom experiments and patient studies. In the phantom experiments, a plastic bottle simulating a face mask was attached to a cylindric phantom simulating the brain. The cylindric phantom was filled with 18F-FDG solution (3.8-7.0 kBq/mL). The bottle was filled with nonradioactive air or various levels of 18F-FDG (0-170 kBq/mL). Images were corrected either by TFS-SSS or MCS-SSS using the CT data of the bottle filled with nonradioactive air. We compared the image activity concentration in the cylindric phantom with the true activity concentration. We also performed 15O-gas brain PET based on the steady-state method on patients with cerebrovascular disease to obtain quantitative images of cerebral blood flow and oxygen metabolism. Results: In the phantom experiments, a cold artifact was observed immediately next to the bottle on TFS-SSS images, where the image activity concentrations in the cylindric phantom were underestimated by 18%, 36%, and 70% at the bottle radioactivity levels of 2.4, 5.1, and 9.7 kBq/mL, respectively. At higher bottle radioactivity, the image activity concentrations in the cylindric phantom were greater than 98% underestimated. For the MCS-SSS, in contrast, the error was within 5% at each bottle radioactivity level, although the image generated slight high-activity artifacts around the bottle when the bottle contained significantly high radioactivity. In the patient imaging with 15O2 and C15O2 inhalation, cold artifacts were observed on TFS-SSS images, whereas no artifacts were observed on any of the MCS-SSS images. Conclusion: MCS-SSS accurately corrected the scatters in 15O-gas brain PET when the 3-dimensional acquisition mode was used, preventing the generation of cold artifacts, which were observed immediately next to a face mask on TFS-SSS images. The MCS-SSS method will contribute to accurate quantitative assessments.

Investigation of optimization-based reconstruction with an image-total-variation constraint in PET.

Interest remains in reconstruction-algorithm research and development for possible improvement of image quality in current PET imaging and for enabling innovative PET systems to enhance existing, and facilitate new, preclinical and clinical applications. Optimization-based image reconstruction has been demonstrated in recent years of potential utility for CT imaging applications. In this work, we investigate tailoring the optimization-based techniques to image reconstruction for PET systems with standard and non-standard scan configurations. Specifically, given an image-total-variation (TV) constraint, we investigated how the selection of different data divergences and associated parameters impacts the optimization-based reconstruction of PET images. The reconstruction robustness was explored also with respect to different data conditions and activity up-takes of practical relevance. A study was conducted particularly for image reconstruction from data collected by use of a PET configuration with sparsely populated detectors. Overall, the study demonstrates the robustness of the TV-constrained, optimization-based reconstruction for considerably different data conditions in PET imaging, as well as its potential to enable PET configurations with reduced numbers of detectors. Insights gained in the study may be exploited for developing algorithms for PET-image reconstruction and for enabling PET-configuration design of practical usefulness in preclinical and clinical applications.

Transmission scan truncation with small-field-of-view dedicated cardiac SPECT systems: impact and automated quality control.

BACKGROUND: Small-field-of-view (FOV) dedicated cardiac single photon emission computed tomography (SPECT) systems will frequently exhibit severe transmission scan truncation that may degrade attenuation correction (AC). This study evaluated the impact of transmission scan truncation on AC and developed automated transmission scan truncation quality control (ATSTQC) for small-FOV systems. METHODS AND RESULTS: Small-FOV data were simulated from the data of 10 patients acquired by a full-FOV Philips Vertex system. AC images of the full- and small-FOV data were compared by mean and maximum absolute differences of myocardial counts, and differences in stress and rest severity scores were calculated by use of the Emory Cardiac Toolbox.small-FOV systems. ATSTQC was developed to identify critical truncation that significantly increased these indices and then tested with 18 independent patients. Left-side truncation resulted in significant distortion of the quantitative indices. ATSTQC, developed on the condition that left-side truncation is critical, showed high concordance with the qualitative assessment in identification of critical truncation. CONCLUSIONS: Identification of left-side truncation as critical truncation is necessary to judge whether accurate AC can be obtained. The developed ATSTQC can accurately detect critical truncation and will help clinicians decide whether to use AC in a particular study.