A Novel Approach for Position Verification and Dose Calculation through Local MVCT Reconstruction.

Traditional positioning verification using cone-beam computed tomography (CBCT) may incur errors due to potential misalignments between the isocenter of CBCT and the treatment beams in radiotherapy. This study introduces an innovative method for verifying patient positioning in radiotherapy. Initially, the transmission images from an electronic portal imaging device (EPID) are acquired from 10 distinct angles. Utilizing the ART-TV algorithm, a sparse reconstruction of local megavoltage computed tomography (MVCT) is performed. Subsequently, this MVCT is aligned with the planning CT via a three-dimensional mutual information registration technique, pinpointing any patient-positioning discrepancies and facilitating corrective adjustments to the treatment setup. Notably, this approach employs the same radiation source as used in treatment to obtain three-dimensional images, thereby circumventing errors stemming from misalignment between the isocenter of CBCT and the accelerator. The registration process requires only 10 EPID images, and the dose absorbed during this process is included in the total dose calculation. The results show that our method's reconstructed MVCT images fulfill the requirements for registration, and the registration algorithm accurately detects positioning errors, thus allowing for adjustments in the patient's treatment position and precise calculation of the absorbed dose.

HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells.

Pancreatic cancer is one of the most malignant tumor types and is characterized by high metastasis ability and a low survival rate. As a chromatin-binding protein, HMGA2 is widely overexpressed and considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that HMGA2 is highly expressed in pancreatic cancer tissues, mainly distributed in epithelial cells, and represents a subtype of high epithelial-mesenchymal transition. Deletion of HMGA2 inhibits tumor malignancy through cell proliferation, metastasis, and xenograft tumor growth in vivo. Moreover, HMGA2 enhanced the cellular redox status by inhibiting reactive oxygen species and promoting glutathione production. Importantly, ferroptotic cell death was significantly ameliorated in cells overexpressing HMGA2. Conversely, HMGA2 deletion exacerbated ferroptosis. Mechanistically, HMGA2 activated GPX4 expression through transcriptional and translational regulation. HMGA2 binds and promotes cis-element modification in the promoter region of the GPX4 gene by enhancing enhancer activity through increased H3K4 methylation and H3K27 acetylation. Furthermore, HMGA2 stimulated GPX4 protein synthesis via the mTORC1-4EBP1 and -S6K signaling axes. The overexpression of HMGA2 alleviated the decrease in GPX4 protein levels resulting from the pharmacologic inhibition of mTORC1. Conversely, compared with the control, HMGA2 deletion more strongly reduced the phosphorylation of 4EBP1 and S6K. A strong positive correlation between HMGA2 and GPX4 expression was confirmed using immunohistochemical staining. We also demonstrated that HMGA2 mitigated the sensitivity of cancer cells to combination treatment with a ferroptosis inducer and mTORC1 inhibition or gemcitabine. In summary, our results revealed a regulatory mechanism by which HMGA2 coordinates GPX4 expression and underscores the potential value of targeting HMGA2 in cancer treatment.

A biosensor for D-2-hydroxyglutarate in frozen sections and intraoperative assessment of IDH mutation status.

The oncometabolite D-2-hydroxyglutarate (D-2-HG) has emerged as a valuable biomarker in tumors with isocitrate dehydrogenase (IDH) mutations. Efficient detection methods are required and rapid intraoperative determination of D-2-HG remains a huge challenge. Herein, D-2-HG dehydrogenase from Achromobacter xylosoxidans (AX-D2HGDH) was found to have high substrate specificity. AX-D2HGDH dehydrogenizes D-2-HG and reduces flavin adenine dinucleotide (FAD) bound to the enzyme. Interestingly, the dye resazurin can be taken as another substrate to restore FAD. AX-D2HGDH thus catalyzes a bisubstrate and biproduct reaction: the dehydrogenation of D-2-HG to 2-ketoglutarate and simultaneous reduction of non-fluorescent resazurin to highly fluorescent resorufin. According to steady-state analysis, a ping-pong bi-bi mechanism has been concluded. The Km values for resazurin and D-2-HG were determined as 0.56 µM and 10.93 µM, respectively, suggesting high affinity to both substrates. On the basis, taking AX-D2HGDH and resazurin as recognition and fluorescence transducing element, a D-2-HG biosensor (HGAXR) has been constructed. HGAXR exhibits high sensitivity, accuracy and specificity for D-2-HG in different biological samples. With the aid of HGAXR and the matched low-cost palm-size detecting device, D-2-HG levels in frozen sections of resected brain tumor tissues can be measured in a direct, simple and accurate manner with a fast detection (1-3 min). As the technique of frozen section is familiar to surgeons and pathologists, HGAXR and the portable device can be easily integrated into the current workflow, having potential to provide rapid intraoperative pathology for IDH mutation status and guide decision-making during surgery.

Interpretation and Prediction of the CO2 Sequestration of Steel Slag by Machine Learning.

The utilization of steel slag for CO2 sequestration is an effective way to reduce carbon emissions. The reactivity of steel slag in CO2 sequestration depends mainly on material and process parameters. However, there are many puzzles in regard to practical applications due to the different evaluations of process parameters and the lack of investigation of material parameters. In this study, 318 samples were collected to investigate the interactive influence of 12 factors on the carbonation reactivity of steel slag by machine learning with SHapley Additive exPlanations (SHAP). Multilayer perceptron (MLP), random forest, and support vector regression models were built to predict the slurry-phase CO2 sequestration of steel slag. The MLP model performed well in terms of prediction ability and generalization with comprehensive interpretability. The SHAP results showed that the impact of the process parameters was greater than that of the material parameters. Interestingly, the iron ore phase of steel slag was revealed to have a positive effect on steel slag carbonation by SHAP analysis. Combined with previous literature, the carbonation mechanism of steel slag was proposed. Quantitative analysis based on SHAP indicated that steel slag had good carbonation reactivity when the mass fractions of "CaO + MgO", "SiO2 + Al2O3", "Fe2O3", and "MnO" varied from 50-55%, 10-15%, 30-35%, and <5%, respectively.

HMGA1 and FOXM1 Cooperate to Promote G2/M Cell Cycle Progression in Cancer Cells.

HMGA1 is a chromatin-binding protein and performs its biological function by remodeling chromatin structure or recruiting other transcription factors. However, the role of abnormally high level of HMGA1 in cancer cells and its regulatory mechanism still require further investigation. In this study, we performed a prognostic analysis and showed that high level of either HMGA1 or FOXM1 was associated with poor prognosis in various cancers based on the TCGA database. Furthermore, the expression pattern of HMGA1 and FOXM1 showed a significant strong positive correlation in most type of cancers, especially lung adenocarcinoma, pancreatic cancer and liver cancer. Further analysis of the biological effects of their high correlation in cancers suggested that cell cycle was the most significant related pathway commonly regulated by HMGA1 and FOXM1. After knockdown of HMGA1 and FOXM1 by specific siRNAs, an obvious increased G2/M phase was observed in the siHMGA1 and siFOXM1 groups compared to the siNC group. The expression levels of key G2/M phase regulatory genes PLK1 and CCNB1 were significantly downregulated. Importantly, HMGA1 and FOXM1 were identified to form a protein complex and co-located in the nucleus based on co-immunoprecipitation and immunofluorescence staining, respectively. Thus, our results provide the basic evidence that HMGA1 and FOXM1 cooperatively accelerate cell cycle progression by up-regulating PLK1 and CCNB1 to promote cancer cell proliferation.

Reducing Radiation Dose and Improving Image Quality in CT Portal Venography Using 80 kV and Adaptive Statistical Iterative Reconstruction-V in Slender Patients.

OBJECTIVE: To explore the feasibility of reducing radiation dose and improving image quality in CT portal venography (CTPV) using 80 kV and adaptive statistical iterative reconstruction-V(ASIR-V) in slender patients in comparison with conventional protocol using 120 kV and ASIR. METHODS: Sixty slender patients for enhanced abdominal CT scanning were randomly divided into group A and group B. Group A used the conventional 120 kV tube voltage, 600 mgI/kg contrast dose and reconstructed with the recommended 40% ASIR. Group B used 80 kV tube voltage, 350 mgI/kg contrast dose and reconstructed with ASIR-V from 40% to 100% with 10% interval. The CT values and standard deviation (SD) values of the main portal vein, left branch, and right branch of portal vein, liver, and erector spinae at the same level were measured to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The image quality was subjectively scored by two experienced radiologists blindly using a 5-point criterion. The contrast dose, volumetric CT dose index, and dose length product were recorded in both groups and the effective dose was calculated. RESULTS: There was no significant difference in general data between the two groups (p > 0.05), the effective dose and contrast dose in group B were reduced by 63.3% (p < 0.001) and 39.7% (p < 0.001), respectively compared with group A. With the percentage of ASIR-V increased in group B, the CT values showed no significant difference, while the SD values gradually decreased and SNR values and CNR values increased accordingly. Compared with group A, group B demonstrated similar CT values (p > 0.05), while the SD values with 80% ASIR-V to 100% ASIR-V were significantly lower than those of 40% ASIR (p < 0.001), and the SNR values and CNR values with 70% ASIR-V to 100% ASIR-V were significantly higher than those of 40% ASIR (p < 0.001). The subjective image quality scores by the two radiologists had excellent consistency (kappa value>0.75, p < 0.001), and the final subjective image quality scores and the subjective scores in each of the 5 scoring categories with 60% ASIR-V to 100% ASIR-V were all significantly higher than those of 40% ASIR, and 80% ASIR-V obtained the highest subjective score among different reconstructions. CONCLUSION: In CTPV, the application of 80 kV and ASIR-V reconstruction in slender patients can significantly reduce radiation dose (by 63.3%) and contrast agent dose (by 39.7%). Compared with the recommended 40% ASIR using 120 kV, ASIR-V with 80% to 100% percentages can further improve image quality and with 80% ASIR-V being the best reconstruction algorithm. ADVANCES IN KNOWLEDGE: CTPV with 80 kV and ASIR-V algorithm in slender patients can significantly reduce radiation dose and contrast agent dose as well as improve image quality, compared with the conventional 120 kV protocol using 40% ASIR.

Application of Adaptive Statistical Iterative Reconstruction-V With Combination of 80 kV for Reducing Radiation Dose and Improving Image Quality in Renal Computed Tomography Angiography for Slim Patients.

OBJECTIVES: To explore the application of adaptive statistical iterative reconstruction-V (ASIR-V) with combination of 80 kV for reducing radiation dose and improving image quality in renal computed tomography angiography (CTA) for slim patients compared with traditional filtered back projection (FBP) reconstruction using 120 kV. METHODS: Eighty patients for renal CTA were prospectively enrolled and randomly divided into group A and group B. Group A used 120 kV and 600 mgI/kg contrast agent and FBP reconstruction, while group B used 80 kV and 350 mgI/kg contrast agent and both FBP and ASIR-V reconstruction from 10%ASIR-V to 100%ASIR-V with 10%ASIR-V interval. The CT values and SD values of the right renal artery and left renal artery were measured to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The image quality was subjectively scored by two experienced radiologists blindly using a five-point criterion. The contrast agent, volumetric CT dose index (CTDIvol), and dose length product in both groups were recorded and the effective radiation dose was calculated. RESULTS: There were no significant difference in patient characteristics between two groups (p > 0.05). The CTDIvol, dose length product and effective radiation dose in group B were 59.0%, 65.0%, and 65.1% lower than those in group A, respectively (all p < 0.05), and the contrast agent in group B was 42.2% lower than that in group A (p < 0.05). In group B, with the increase of ASIR-V percentage, CT values showed no significant difference, SD values decreased gradually, SNR values and CNR values increased gradually. The CT values showed no statistically significant difference (p > 0.05) between two groups with different reconstructions. The SD values with 40%ASIR-V to 100%ASIR-V reconstruction in group B was significantly lower(p < 0.5), while the SNR values with 50% ASIR-V to 100% ASIR-V reconstruction and CNR values with 70%ASIR-V to 100%ASIR-V were significantly higher than those of group A with FBP reconstruction (p < 0.5). Two radiologists had excellent consistency in subjective scores of image quality for renal CTA (kappa >0.75, p < 0.05). The subjective scores with 60% ASIR-V to 90% ASIR-V in group B were significantly higher than those of FBP in group A (p < 0.5), of which 70%ASIR-V reconstruction obtained the highest subjective score for renal CTA. CONCLUSION: ASIR-V with combination of 80 kV can significantly reduce effective radiation dose (about 65.1%) and contrast agent (about 42.2%) and improve image quality in renal CTA for slim patients compared with traditional FBP reconstruction using 120 kV, and the 70% ASIR-V was the best reconstruction algorithm in 80 kV renal CTA. ADVANCES IN KNOWLEDGE: Using 80 kV with combination of ASIR-V can significantly reduce radiation dose and contrast agent dose as well as improve image quality in renal CTA for thin patients when compared with FBP using 120 kV.

Differential diagnosis between benign and malignant pleural effusion with dual-energy spectral CT.

PURPOSE: To investigate the value of spectral CT in the differential diagnosis of benign from malignant pleural effusion. METHOD AND MATERIALS: 14 patients with benign pleural effusion and 15 patients with malignant pleural effusion underwent non-contrast spectral CT imaging. These patients were later verified by the combination of disease history, clinical signs and other information with the consensus of surgeons and radiologists. Various Spectral CT image parameters measured for the effusion were as follows: CT numbers of the polychromatic 140kVp images, monochromatic images at 40keV and 100keV, the material density contents from the water, fat and blood-based material decomposition images, the effective atomic number and the spectral curve slope. These values were statistically compared with t test and logistic regression analysis between benign and malignant pleural effusion. RESULTS: The CT value of benign and malignant pleural effusion in the polychromatic 140kVp images showed no differences (12.61±3.39HU vs. 14.71±5.03HU) (P>0.05), however, they were statistically different on the monochromatic images at 40keV (43.15±3.79 vs. 39.42±2.60, p = 0.005) and 100keV (9.11±1.38 vs. 6.52±2.04, p<0.001). There was difference in the effective atomic number value between the benign (7.87±0.08) and malignant pleural effusion (7.90±0.02) (P = 0.02). Using 6.32HU as the threshold for CT value measurement at 100keV, one could obtain sensitivity of 100% and specificity of 66.7% with area-under-curve of 0.843 for differentiating benign from malignant effusion. In addition, age and disease history were potential confounding factors for differentiating malignant pleural effusion from benign, since the older age (61.13±12.51 year-old vs48.57±12.33 year-old) as well as longer disease history (70.00±49.28 day vs.28.36±21.64 day) were more easily to be found in the malignant pleural effusion group than those in the benign pleural effusion group. By combining above five factors, one could obtain sensitivity of 100% and specificity of 71.4% with area-under-curve of 0.933 for differentiating benign from malignant effusion. CONCLUSION: The CT value measurement at both high and low energy levels and the effective atomic number obtained in a single spectral CT scan can assist the differential diagnosis of benign from malignant pleural effusion.Combining them with patient age and disease history can further improve diagnostic performance. CLINICAL RELEVANCE/APPLICATION: Clinical findings and Spectral CT imaging can provide significant evidences about the nature of pleural effusion.

Clinical value of dual-energy spectral imaging with adaptive statistical iterative reconstruction for reducing contrast medium dose in CT portal venography: in comparison with standard 120-kVp imaging protocol.

OBJECTIVE: To evaluate the clinical value of dual-energy spectral CT with adaptive statistical iterative reconstruction (ASiR) for reducing contrast medium dose in CT portal venography (CTPV). METHODS: This prospective study was institutional review board-approved, and written informed consent was obtained from all patients. 50 patients undergoing abdominal CT were randomized to 2 groups: Group A (n = 25), using spectral CT and 350 mgI kg(-1) contrast injection protocol; Group B (n = 25), using standard 120 kVp and 500 mgI kg(-1) contrast. Spectral CT images at 60 keV and standard 120-kVp images were both reconstructed with 50% ASiR. CT number and contrast-to-noise ratio (CNR) for intrahepatic and extrahepatic portal veins were measured. The maximum intensity projection (MIP) and volume-rendering (VR) images were used for subjective evaluation. These two kinds of results were statistically analyzed. RESULTS: CNR values for the intrahepatic portal vein of the 60-keV spectral images (4.2 ± 1.1) were higher than those of 120-kVp images (3.0 ± 2.1) (p = 0.03) and were the same for the extrahepatic portal vein (5.9 ± 1.4 vs 5.9 ± 1.6, p = 0.90). The portal vein and left and right branches in the 60-keV spectral images had higher CT number and lower standard deviation than the 120-kVp images (p < 0.05). Radiation dose (dose-length product and effective dose) and subjective image quality were similar for the two groups, while the spectral CT group required 25% less iodine dose (23.1 ± 3.2 g vs 30.5 ± 5.0 g). CONCLUSION: The 60-keV spectral CT images with ASiR allow 25% reduction in the iodine dose while providing better or equal image quality as the standard 120-kVp images in portal venography with comparable radiation dose. ADVANCES IN KNOWLEDGE: Compared with conventional 120-kVp CT, the use of 60-keV spectral CT images provides 25% contrast dose reduction with similar image quality in CTPV. Compared with conventional 120-kVp CT, the use of 60-keV spectral CT images with ASiR algorithm improves CNR values for the intrahepatic portal vein.